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Lab presentation

We investigate the structural enzymology and chemical biology of proteins involved in the biosynthesis, degradation and modification of glycans. We use a multidisciplinary approach including X-ray Crystallography, X-ray Free Electron Laser (XFEL), Cryo Electron Microscopy (Cryo-EM), Small Angle X-ray Scattering, Protein Biophysics, Protein Biochemistry and Molecular Biology, to elucidate mechanistic aspects of these processes at the molecular level of detail.

Projects

Glycans are not only one of the major components of the cell but also are essential molecules that modulate a variety of important biological processes in all living organisms. Glycans are used primarily as energy storage and metabolic intermediates as well as being main structural constituents in bacteria and plants. Moreover, as a consequence of protein and lipid glycosylation, glycans generate a significant amount of structural diversity in biological systems. This structural information is particularly apparent in molecular recognition events including cell-cell interactions during critical steps of development, the immune response and host-pathogen interactions.

In that context, research is concentrated – but not limited – on:

  1. Rationalizing glycoengineering strategies for immunotherapeutic antibodies.
  2. Unveiling the role of gut microbiota in health and disease.
  3. The cell envelope in bacterial physiology and pathogenesis.
  4. Understanding and engineering substrate specificity of Carbohydrate Active enZymes.

 You will find detailed information at https://sites.google.com/site/guerinlab/home

Lab people

My interest in Glycobiology began as an undergraduate student, working in glycoside hydrolases under professor Alberto C. Frasch at the Leloir Institute, Buenos Aires, Argentina (1991-1996). This research center was named in honor to Luis F. Leloir, who discovered the first sugar nucleotide and was awarded the Nobel Prize in Chemistry in 1970 for his fundamental contributions to our current knowledge of glycan biosynthesis and metabolism. I then completed my doctoral studies in the area of chemistry, mainly using biochemistry, molecular biology and glycobiology techniques, under professor Armando J. Parodi. I studied mechanistic aspects of the UDP-Glc:glycoprotein glucosyltransferase, an exquisite enzyme that senses the folding status of substrate glycoproteins in the endoplasmic reticulum (1997-2002). During that time, in the late 1990s, three-dimensional structural information of glycosyltransferases was very limited, in part because they are frequently membrane-associated.

To further advance towards the understanding of the molecular mechanisms that govern glycosyl transfer reactions, I moved to professor Pedro M. Alzari’s laboratory, at the Structural Biochemistry Unit, Institut Pasteur, Paris, France, where I was first introduced to macromolecular X-ray crystallography and protein biophysics (2003-2007). Of particular relevance in the field, we reported the very first crystal structures of a glycogen synthase and that of the essential membrane-associated phosphatidylinositol mannosyltransferase PimA, a key glycosyltranferase involved in the biosynthesis of mycobacterial phosphatidylinositol mannosides. After this postdoctoral stage, I continued my work on the biosynthesis of mycobacterial cell envelope glycoconjugates, when I transferred as a postdoctoral fellow under professor Mary Jackson, at the Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, United States (2008-2009).

In November 2009, I was awarded an Ikerbasque Research Professor position and group leader of the Structural Glycobiology Laboratory (2009-2023). In June 2023, I was awarded with a Research Professor position from the Spanish National Research Council (CSIC) to establish and further progress my group at the Institute of Molecular Biology of Barcelona (IBMB), Spain. Recent publications are in top-ranking journals including Nature Chemical Biology, Nature Communications, Science Advances, Angewandte Chemie Int. Ed., Proceedings National Academy Sciences USA, EMBO J, Current Opinion Structural Biology, PLoS Pathogens, Structure, ACS Central Science, ACS Chemical Biology, Nucleic Acids Research and the Journal of Biological Chemistry between others. I am currently an Editorial Board Member of the Journal of Biological Chemistry (2023-2027). IBMB is the largest research center of CSIC focused on Life and Medical Sciences in Catalonia, Spain. The IBMB is currently located in the Barcelona Science Park (PCB), providing an outstanding scientific and multidisciplinary environment, and state-of-the-art facilities. In 2015, the DSB received the Excellence Award “María de Maeztu” from the Spanish Ministry of Science and Innovation, earning a place alongside the top research Structural Biology units in Spain.

Selected publications

  1. Angala SK, Carreras-Gonzalez A, Huc-Claustre E, Anso I, Kaur D, Jones V, Palčeková Z, Belardinelli JM, Sousa-d’Auria C, Shi L, Slama N, Houssin C, Quémard A, McNeil M, Guerin ME, Jackson M. A unique pathway to the acylation of glycerolipids in mycobacteria. Nat. Commun. 14:6694 (2023). doi: 10.1038/s41467-023-42478-x

  1. Franklin A, Layton A, Mize T, Salgueiro VC, Sullivan R, Benedict S, Gurcha SS, Anso I, Besra GS, Banzhaf M, Lovering AL, Williams S, Guerin ME, Scott N, Prados-Rosales R, Lowe E, Moynihan PJ. The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth. bioRxiv. 10.1101/2023.10.26.563968 (2023). doi: 10.1101/2023.10.26.563968

  1. Guerin ME. Trapping and retaining intermediates in glycosyltransferases. J. Biol. Chem. 299(8):105006 (2023). doi: 10.1016/j.jbc.2023.105006

  1. Han X, D’Angelo C, Otamendi A, Cifuente JO, de Astigarraga E, Ochoa-Lizarralde B, Grininger M, Routier FH, Guerin ME, Fuehring J, Etxebeste O, Connell SR. CryoEM analysis of the essential native UDP-glucose pyrophosphorylase from Aspergillus nidulans reveals key conformations for activity regulation and function. mBio. 14(4):e0041423 (2023). doi: 10.1128/mbio.00414-23

  1. García-Alija M, van Moer B, Sastre DE, Azzam T, Du JJ, Trastoy B, Callewaert N, Sundberg EJ, Guerin ME*. Modulating antibody effector functions by Fc glycoengineering. Biotechnology Adv. 67:108201.108201 (2023). Review. doi: 10.1016/j.biotechadv.2023.108201

  1. Cifuente JO, Schulze J, Di Domenico V, Bethe A, Litschko C, Budde I, Eidenberger L, Thiesler H, Ramon Roth I, Berger M, Claus H, D’Angelo C, Marina A, Gerardy-Schahn R, Schubert M, Guerin ME*, and Fiebig T. A multi-modular enzymatic machine polymerizes the Haemophilus influenzae capsule. Nat. Chem. Biol. 19:865-877 (2023). Highlighted in the News and Views section: Basket of sweets. Dorfmueller HC. Nat. Chem. Biol. 19:795-796 (2023). doi: 10.1038/s41589-023-01324-3

  1. Anso I, Naegeli A, Cifuente JO, Orrantia A, Andersson E, Moraleda-Montoya A, García-Alija M, Corzana F, Del Orbe RA, Borrego F, Trastoy B, Sjögren J, Guerin ME*. Turning universal O into rare Bombay type blood. Nat. Commun. 14(1):1765 (2023). doi: 10.1038/s41467-023-37324-z

  1. Trastoy B, Du JJ, Cifuente JO, Rudolph L, García-Alija M, Klontz E, Deredge D, Sultana N, Huynh CG, Flowers M, Li C, Sastre D, Wang LX, Corzana F, Mallagaray A, Sundberg EJ, Guerin ME*. Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases. Nat. Commun. 14(1):1705 (2023). doi: 10.1038/s41467-023-37215-3

  1. Cioetto-Mazzabò L, Boldrin F, Beauvineau C, Marina A, Speth M, Namouchi A, Cimino M, Favre-Rochex S, Segafreddo G, Balasingham S, Trastoy B, Munier-Lehmann H, Griffiths G, Gicquel B, Guerin ME, Manganelli R, Alonso-Rodríguez N. SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression. Nucl. Acids Res. 51(1):144-165 (2023). doi: 10.1093/nar/gkac1173

  1. Cordeiro RL, Santos CR, Domingues MN, Lima TB, Pirolla RAS, Morais MAB, Colombari FM, Miyamoto RY, Persinoti GF, Borges AC, Stoffel F, Li C, Gozzo FC, van Heel M, Guerin ME, Sundberg EJ, Wang L-X, Portugal RV, Giuseppe PO, Murakami MT. Mechanisms of high-mannose N-glycan breakdown and metabolism by the human gut commensal Bifidobacterium longum. Nat. Chem. Biol. 19(2):218-229 (2022). Highlighted in the News and Views section: A sweet feast. Crouch LI. 19(2):131-132. Nat. Chem. Biol. (2023). doi: 10.1038/s41589-022-01202-4

  1. García-Alija M, Du JJ, Ordóñez I, Diz-Vallenilla A, Moraleda-Montoya A, Sultana N, Huynh C, Li C, Donahue T, Wang L-X., Trastoy B, Sundberg EJ, Guerin ME*. Mechanism of cooperative N-glycan processing by the multi-modular endoglycosidase EndoE. Nat. Commun. 13:1137 (2022). doi: 10.1038/s41467-022-28722-w

  1. Trastoy B, Du JJ, García-Alija M, Li C, Klontz EH, Wang LX, Sundberg EJ, Guerin ME*. Sculpting N-glycosylation of therapeutic monoclonal antibodies by the use of specific endoglycosidases. Curr. Opin. Struct. Biol. 72:248-259. Highlighted as a Faculty Opinions article (2022). Review. doi: 10.1016/j.sbi.2021.11.016

  1. Anso I, Basso LGM, Wang L, Marina A, Páez-Pérez ED, Jäger C, Gavotto F, Tersa M, Perrone S, Contreras F.-X, Prandi J, Gilleron M, Linster CL, Corzana F, Lowary TL, Trastoy B, Guerin ME*. Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA. Sci. Adv. 7:eabj4565 (2021). doi: 10.1126/sciadv.abj4565

  1. Trastoy B, Du JJ, Li C, García-Alija M, Klontz EH, Roberts BR, Donahue TC, Wang LX, Sundberg EJ, Guerin ME*. GH18 endo-β-N-acetylglucosaminidases use distinct mechanisms to process hybrid-type N-linked glycans. J. Biol. Chem. 297:101011 (2021). doi: 10.1016/j.jbc.2021.101011

  1. Boldrin F, Anso I, Alebouyeh S, Sevilla IA, Geijo M, Garrido JM, Marina A, Cioetto Mazzabò L, Segafreddo G, Guerin ME, Manganelli R, Prados-Rosales R. The phosphatidyl-myo-inositol dimannoside acyltransferase PatA is essential for Mycobacterium tuberculosis growth in vitro and in vivo. J. Bacteriol. 203:e00439-20 (2021). doi: 10.1128/jb.00439-20

  1. Trastoy B, Anso I, Naegeli A, Sjögren J, Guerin ME*. Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila. Nat. Commun. 11:4844 (2020). doi: 10.1038/s41467-020-18696-y

  1. Liebau J, Tersa M, Trastoy B, Patrick J, Rodrigo-Unzueta A, Sparrman T, Guerin ME*, Mäler L. Unveiling the activation dynamics of a fold-switch bacterial glycosyltransferase by 19F NMR. J. Biol. Chem. 295:9868-9878 (2020). doi: 10.1074/jbc.RA120.014162

  1. Trastoy B, Du JJ, Klontz EH, Li C, Cifuente JO, Wang LX, Sundberg EJ, Guerin ME*. Structural basis of mammalian high-mannose N-glycans processing by human gut Bacteroides. Nat. Commun. 11:899 (2020). Highlighted as F1000Prime article (2020). doi: 10.1038/s41467-020-14754-7

  1. Rodrigo-Unzueta A, Ghirardello M, Urresti S, Delso I, Giganti D, Anso I, Trastoy B, Comino N, Tersa M, D’Angelo C, Cifuente JO, Marina A, Liebau J, Mäler L, Chenal A, Albesa-Jové D, Merino P, Guerin ME*. Dissecting the structural and chemical determinants of the ‘open-to-closed’ motion in the mannosyltransferase PimA from mycobacteria. Biochemistry 59(32): 2934-2945 (2020). doi: 10.1021/acs.biochem.0c00376

  1. Cifuente JO, Comino N, D’Angelo C, Marina A, Gil-Carton D, Albesa-Jové D, Guerin ME*. The allosteric control mechanism of bacterial glycogen biosynthesis disclosed by cryoEM. Curr. Res. Struct. Biol. 2:89-103 (2020). doi: 10.1016/j.crstbi.2020.04.005

  1. Sastre DM, Basso LGM, Trastoy B, Contreras X, Gueiros-Filho F, de Mendoza D, Navarro MVAS, Guerin ME*. Membrane fluidity adjusts the insertion and activity of the transacylase PlsX to regulate phospholipid biosynthesis in Gram positive bacteria. J. Biol. Chem. 295:2136-2147 (2020). Highlighted in the Lipid News section of ASBMB Today (2020). doi: 10.1074/jbc.ra119.011122

  1. Du JJ, Klontz EH, Guerin ME, Trastoy B, Sundberg EJ. Structural insights into the mechanisms and specificities of IgG-active endoglycosidases. Glycobiology 30(4):268-279 (2020). Review. doi: 10.1093/glycob/cwz042

  1. Grifoll-Romero L, Sainz-Polo MA, Albesa-Jové D, Guerin ME, Biarnés X, Planas A. Structure-function relationships underlying the dual N-acetylmuramic and N-acetylglucosamine specificities of the peptidoglycan deacetylase PdaC from Bacillus subtilis. J. Biol. Chem. 294(50):19066-19080 (2019). doi: 10.1074/jbc.ra119.009510

  1. Klontz, EH, Trastoy B, Deredge D, Fields JK, Orwenyo J, Beadenkopf R, Günther S, Flores J, Wintrode P, Wang LX, Guerin ME*, Sundberg EJ. Molecular basis of broad spectrum N-glycan specificity and processing of therapeutic IgG monoclonal antibodies by Endoglycosidase S2. ACS Cent. Sci. 5(3):524-538 (2019). Highlighted as F1000Prime article (2019). doi: 10.1021/acscentsci.8b00917

  1. Paczia N, Becker-Kettern J, Conrotte JF, Cifuente JO, Guerin ME, Linster CL. 3-Phosphoglycerate transhydrogenation instead of dehydrogenation alleviates redox state dependency of yeast de novo L-serine synthesis. Biochemistry 58(4):259-275 (2019). doi: 10.1021/acs.biochem.8b00990

  1. Cifuente JO, Comino N, Trastoy, B, D’Angelo C, Guerin ME*. Structural basis of glycogen metabolism in bacteria. Biochem. J. 476(14):2059-2092 (2019). Review. doi: 10.1042/bcj20170558

  1. Kalscheuer R, Palacios A, Anso I, Anguita J, Jacobs Jr. WR, Guerin ME, Prados-Rosales R. The Mycobacterium tuberculosis capsule: a cell structure with key implications in pathogenesis. Biochem. J. 476(14):1995-2016 (2019). Review. doi: 10.1042%2FBCJ20190324

  1. Albesa-Jové D, Cifuente JO, Trastoy B, Guerin ME*. Quick-soaking of crystals reveals unprecedented insights into the catalytic mechanism of glycosyltransferases. Methods Enzymol. 621:261-279 (2019). Review. doi: 10.1016/bs.mie.2019.02.034

  1. Cabrera Y, Dublanga L, Fernández-Higuero JA, Albesa-Jové D, Lucas M, Viguera AR, Guerin ME, Vilar JMG, Muga A, Moro F. Regulation of human Hsc70 ATPase and chaperone activities by Apg2: role of the acidic subdomain. J. Mol. Biol. 431(2):444-461 (2019). doi: 10.1016/j.jmb.2018.11.026

  1. Guerin ME, Stirnemann G, Giganti D. Conformational entropy of a single peptide controlled under force governs protease recognition and catalysis. Proc. Natl. Acad. Sci. USA 115(45):11525-11530 (2018). doi: 10.1073/pnas.1803872115

  1. Trastoy B, Klontz E, Orwenyo J, Marina A, Wang LX, Sundberg EJ, Guerin ME*. Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S. Nat. Commun. 9(1):1874 (2018). doi: 10.1038/s41467-018-04300-x

  1. Tersa T, Raich L, Albesa-Jové D, Trastoy B, Prandi J, Gilleron M, Rovira C, Guerin ME*. The molecular mechanism of substrate recognition and catalysis of the membrane acyltransferase PatA. ACS Chem. Biol. 13(1):131-140 (2018). doi: 10.1021/acschembio.7b00578

  1. Albesa-Jové D, Sainz-Polo MA, Marina A, Guerin ME*. Structural snapshots of the reaction center of α1,3-galactosyltransferase with native substrates support a conserved catalytic mechanism for retaining glycosyltransferases. Angew Chem Int Ed Engl. 56(47):14853-14857 (2017). doi: 10.1002/anie.201707922

  1. Rosado LA, Wahni K, De Giacomi G, Pedre B, Young D, de la Rubia AG, Boldrin F, Martens E, Marcos-Pascual L, Sancho-Vaello E, Albesa-Jové D, Provvedi R, Martin C, Makarov V, Versees W, Verniest G, Guerin ME, Mateos LM, Manganelli R, Messens J. The antibacterial prodrug activator Rv2466c is a mycothiol-dependent reductase in the oxidative stress response of Mycobacterium tuberculosis. J. Biol. Chem. 292(32):13097-13110 (2017). doi: 10.1074/jbc.m117.797837

  1. Albesa-Jové D, Romero-García J, Sancho-Vaello E, Contreras F-X, Rodrigo-Unzueta A, Comino N, Carreras-González A, Arrasate P, Urresti S, Biarnés X, Planas A, Guerin ME*. Structural snapshots and loop dynamics along the catalytic cycle of glycosyltransferase GpgS. Structure 25(7):1034-1044 (2017). doi: 10.1016/j.str.2017.05.009

  1. Comino N, Cifuente JO, Marina A, Orrantia A, Eguzquiza A, Guerin ME*. Mechanistic insights into the allosteric regulation of bacterial ADP-glucose pyrophosphorylases. J. Biol. Chem. 292(15):6255-6268 (2017). doi: 10.1074/jbc.m116.773408

  1. Sancho-Vaello E, Albesa-Jové D, Rodrigo-Unzueta A, Guerin ME*. Structural basis of phosphatidyl-myo-inositol mannosides biosynthesis in mycobacteria. Biochem. Biophys. Acta. 1862(11):1355-1367 (2017). Review. doi: 10.1016/j.bbalip.2016.11.002

  1. Cifuente JO, Comino N, Madariaga-Marcos J, López-Fernández S, Garcia-Alija M, Agirre J, Albesa-Jové, Guerin ME*. Structural basis of glycogen biosynthesis regulation in bacteria. Structure 24(9):1613-1622 (2016). doi: 10.1016/j.str.2016.06.023

  1. Albesa-Jové D, Guerin ME*. The conformational plasticity of glycosyltransferases. Curr. Opin. Struct. Biol. 40:23-32 (2016). Review. doi: 10.1016/j.sbi.2016.07.007

  1. Rodrigo-Unzueta A, Martínez MA, Comino N, Alzari PM, Chenal A, Guerin ME*. Molecular basis of membrane association by the phosphatidylinositol mannosyltransferase PimA from mycobacteria. J. Biol. Chem. 291(27):13955-13963 (2016). doi: 10.1074/jbc.m116.723676

  1. Albesa-Jové D, Svetlíková Z, Tersa M, Sancho-Vaello E, Carreras-González A, Bonnet P, Arrasate P, Angala SK, Cifuente JO, Korduláková J, Jackson M, Mikušová K, Guerin ME*. Structural basis for selective recognition of acyl chains by the integral membrane associated acyltransferase PatA. Nat. Commun. 7:10906 (2016). doi: 10.1038/ncomms10906

  1. Albesa-Jové D, Comino N, Tersa M, Mohorko E, Urresti S, Dainese E, Chiarelli LR, Pasca MR, Manganelli R, Makarov V, Riccardi G, Svergun I, Glockshuber R, Guerin ME*. The redox state regulates the conformation of Rv2466c to activate TP053 and kill Mycobacterium tuberculosis. J. Biol. Chem. 290(52):31077-31089 (2015). doi: 10.1074/jbc.m115.677039

  1. Albesa-Jové D, Mendoza F, Rodrigo-Unzueta A, Gomollón-Bel F, Cifuente JO, Urresti S, Comino N, Gómez H, Romero-García J, Lluch JM, Sancho-Vaello E, Biarnés X, Planas A, Merino P, Masgrau L Guerin ME*. A native ternary complex trapped in crystal reveals the catalytic mechanism of a retaining glycosyltransferase. Angew Chem Int Ed Engl. 54(34):9898-9902 (2015). doi: 10.1002/anie.201504617

  1. Giganti D, Albesa-Jové D, Urresti S, Rodrigo-Unzueta A, Martínez MA, Comino N, Barilone N, Bellinzoni M, Chenal A, Guerin ME*, Alzari PM. Secondary structure reshuffling modulates glycosyltransferase function at the membrane. Nat. Chem. Biol. 11(1):16-18 (2015). Highlighted in the News and Views section: Membrane enzymes: transformers at the interface. Brodhun F, Tittmann K. Nat. Chem. Biol. 11:102-103 (2015). doi: https://doi.org/10.1038/nchembio.1694

  1. Andrés E, Albesa-Jové D, Biarnés X, Moerschbacher BM, Guerin ME*, Planas A. Structural basis of chitin oligosaccharide deacetylation. Angew Chem Int Ed Engl. 53(27):6882-6887 (2014). doi: 10.1002/anie.201400220

  1. Albesa-Jové D, Chiarelli LR, Makarov V, Pasca MR, Urresti S, Mori G, Salina E, Vocat A, Comino N, Mohorko E, Ryabova S, Pfieiffer B, Lopes Ribeiro AL, Rodrigo-Unzueta A, Tersa M, Zanoni G, Buroni S, Altmann KH, Hartkoorn RC, Glockshuber R, Cole ST, Riccardi G, Guerin ME*. Rv2466c mediates the activation of TP053 to kill replicating and non-replicating Mycobacterium tuberculosis. ACS Chem. Biol. 9(7):1567-1575 (2014). Editor’s choice. doi: 10.1021/cb500149m

  1. Albesa-Jové D, Giganti D, Jackson M, Alzari PM, Guerin ME*. Structure-function relationships of membrane-associated GT-B glycosyltransferases. Glycobiology 24(2):108-124 (2014). Review. doi: 10.1093/glycob/cwt101

  1. Boldrin F, Ventura M, Degiacomi G, Ravishankar S, Sala C, Svetlikova Z, Ambady A, Dhar N, Kordulakova J, Zhang M, Serafini A, Vishwas KG, Kolly GS, Kumar N, Palù G, Guerin ME, Mikusova K, Cole ST, Manganelli R. The phosphatidyl-myo-inositol mannosyltransferase PimA is essential for Mycobacterium tuberculosis growth in vitro and in vivo. J. Bacteriol. 196(19):3441-3451 (2014). doi: 10.1128/jb.01346-13

  1. Giganti D, Alegre-Cebollada J, Urresti S, Albesa-Jove D, Rodrigo-Unzueta A, Comino N, Kachala M, Lopez-Fernandez S, Svergun DI, Fernandez JM, Guerin ME.* Conformational plasticity of the essential membrane associated mannosyltransferase PimA from mycobacteria. J. Biol. Chem. 288(41):29797-29808 (2013). doi: 10.1074/jbc.m113.462705

  1. Albanesi D, Reh G, Guerin ME, Schaeffer F, Debarbouille M, Buschiazzo A, Schujman G, de Mendoza D, Alzari PM. Structural basis for feed-forward transcriptional regulation of membrane lipid homeostasis in Staphylococcus aureus. PLoS Pathog. 9(1):e1003108 (2013). doi: 10.1371/journal.ppat.1003108

  1. Urresti S, Albesa-Jove D, Schaeffer F, Gest P, Pham HT, van der Woerd M, Carreras-Gonzalez A, Lopez-Fernandez S, Brennan PJ, Alzari PM, Jackson M, Guerin ME*. Mechanistic insights into the retaining glucosyl-3-phosphoglycerate synthase GpgS from Mycobacterium tuberculosis. J. Biol. Chem. 287(29):24649-24661 (2012). doi: 10.1074/jbc.M112.368191

  1. Santangelo MP, Gest PM, Guerin ME, Coincon M, Pham H, Ryan G, Puckett SE, Spencer JS, Gonzalez-Juarrero M, Daher R, Lenaerts AJ, Schnappinger D, Therisod M, Ehrt S, Sygusch J, Jackson M. Glycolytic and non-glycolytic functions of the fructose-1,6-bisphosphate aldolase of Mycobacterium tuberculosis, an essential enzyme produced by replicating and persistent bacilli. J. Biol. Chem. 286(46):40219-40231 (2011). doi: 10.1074/jbc.m111.259440

  1. Guerin ME*, Korduláková J, Alzari PM, Brennan PJ, Jackson M. Molecular basis of phosphatidylinositol mannosides biosynthesis and regulation in mycobacteria. J. Biol. Chem. 285(44):33577-33583 (2010). Review. doi: 10.1074/jbc.R110.168328

  1. Daher R, Coincon M, Fonvielle M, Gest P, Guerin ME, Jackson M, Sygusch J, Therisod M. Rational design, synthesis and evaluation of new selective inhibitors of microbial class II (zinc dependent) fructose bis-phosphate aldolases. J. Med. Chem. 53(21):7836-7842 (2010). doi: 10.1021%2Fjm1009814

  1. Guerin ME*, Kaur D, Somashekar BS, Gibbs S, Gest P, Chatterjee D, Brennan P, Jackson M. Insight into the molecular mechanism of the early steps of phosphatidylinositol mannosides biosynthesis in mycobacteria. J. Biol. Chem. 284(38):25687-25696 (2009). doi: 10.1074/jbc.M109.003947

  1. Guerin ME*, Schaeffer F, Chaffotte A, Gest P, Giganti D, Korduláková J, van der Woerd M, Jackson M, Alzari PM. Substrate-induced conformational changes in the essential peripheral-membrane binding mannosyltransferase PimA from mycobacteria. Implications for catalysis. J. Biol. Chem. 284(32):21613-21625 (2009).

  1. Kaur D, Guerin ME, Skovierová H, Brennan PJ, Jackson M. Biogenesis of glycoconjugates in Mycobacterium tuberculosis. Adv. Appl. Microbiol. 69:23-78 (2009). Review. doi: 10.1016%2FS0065-2164(09)69002-X

  1. Stadthagen G, Sambou T, Guerin ME, Barilone N, Boudou F, Korduláková J, Charles P, Alzari PM, Lemassu A, Daffé M, Puzo G, Gicquel B, Rivière M, Jackson M. Genetic bases for the biosynthesis of methylglucose lipopolysaccharides in Mycobacterium tuberculosis. J. Biol. Chem. 282(37):27270-27276 (2007). doi: 10.1074/jbc.m702676200

  1. Guerin ME, Korduláková J, Schaeffer F, Svetliková Z, Buschiazzo A, Giganti D, Gicquel B, Mikusová K, Jackson M, Alzari PM. Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria. J. Biol. Chem. 282(28):20705-20714 (2007). doi: 10.1074/jbc.m702087200

  1. Schujman GE*, Guerin ME*, Buschiazzo A, Schaeffer F, Llarrull L, Reh G, Vila AJ, Alzari PM, de Mendoza D. Structural basis of lipid biosynthesis regulation in Gram-positive bacteria. EMBO J. 25(17):4074-4083 (2006). * These authors contributed equally to this work. doi: 10.1038/sj.emboj.7601284

  1. Buschiazzo A, Ugalde JE, Guerin ME, Ugalde RA, Sheppard W, Alzari PM. Structure of glycogen synthase: homologous enzymes catalyze glycogen synthase and degradation. EMBO J. 23(16):3196-3205 (2004). Highlighted in the ESRF Highlights 2004. doi: 10.1038/sj.emboj.7600324

  1. Guerin ME, Parodi, A.J. The UDP-glucose:glycoprotein glucosyltransferase is organized in at least two tightly bound domains from yeast to mammals. J. Biol. Chem. 278(23):20540-20546 (2003). doi: 10.1074/jbc.M300891200

All publications

  1. Angala SK, Carreras-Gonzalez A, Huc-Claustre E, Anso I, Kaur D, Jones V, Palčeková Z, Belardinelli JM, Sousa-d’Auria C, Shi L, Slama N, Houssin C, Quémard A, McNeil M, Guerin ME, Jackson M. A unique pathway to the acylation of glycerolipids in mycobacteria. Nat. Commun. 14:6694 (2023). doi : 10.1038/s41467-023-42478-x

  1. Franklin A, Layton A, Mize T, Salgueiro VC, Sullivan R, Benedict S, Gurcha SS, Anso I, Besra GS, Banzhaf M, Lovering AL, Williams S, Guerin ME, Scott N, Prados-Rosales R, Lowe E, Moynihan PJ. The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth. bioRxiv. 10.1101/2023.10.26.563968 (2023). doi: 10.1101/2023.10.26.563968

  1. Guerin ME. Trapping and retaining intermediates in glycosyltransferases. J. Biol. Chem. 299(8):105006 (2023). doi: 10.1016/j.jbc.2023.105006

  1. Han X, D’Angelo C, Otamendi A, Cifuente JO, de Astigarraga E, Ochoa-Lizarralde B, Grininger M, Routier FH, Guerin ME, Fuehring J, Etxebeste O, Connell SR. CryoEM analysis of the essential native UDP-glucose pyrophosphorylase from Aspergillus nidulans reveals key conformations for activity regulation and function. mBio. 14(4):e0041423 (2023). doi: 10.1128/mbio.00414-23

  1. García-Alija M, van Moer B, Sastre DE, Azzam T, Du JJ, Trastoy B, Callewaert N, Sundberg EJ, Guerin ME*. Modulating antibody effector functions by Fc glycoengineering. Biotechnology Adv. 67:108201 (2023). Review. doi: 10.1016/j.biotechadv.2023.108201

  1. Cifuente JO, Schulze J, Di Domenico V, Bethe A, Litschko C, Budde I, Eidenberger L, Thiesler H, Ramon Roth I, Berger M, Claus H, D’Angelo C, Marina A, Gerardy-Schahn R, Schubert M, Guerin ME*, and Fiebig T. A multi-modular enzymatic machine polymerizes the Haemophilus influenzae capsule. Nat. Chem. Biol. 19:865-877 (2023). Highlighted in the News and Views section: Basket of sweets. Dorfmueller HC. Nat. Chem. Biol. 19:795-796 (2023). doi: 10.1038/s41589-023-01324-3

  1. Du JJ, Sastre D, Trastoy B, Roberts B, Deredge D, Klontz EH, Flowers MW, Sultana N, Guerin ME, Sundberg EJ. Mass spectrometry-based methods to determine the substrate specificities and kinetics of N-linked glycan hydrolysis by endo-β-N-acetylglucosaminidases. Methods Mol. Biol. 2674:147-167 (2023). Review. doi: 10.1007/978-1-0716-3243-7_10

  1. Anso I, Naegeli A, Cifuente JO, Orrantia A, Andersson E, Moraleda-Montoya A, García-Alija M, Corzana F, Del Orbe RA, Borrego F, Trastoy B, Sjögren J, Guerin ME*. Turning universal O into rare Bombay type blood. Nat. Commun. 14(1):1765 (2023). doi: 10.1038/s41467-023-37324-z

  1. Trastoy B, Du JJ, Cifuente JO, Rudolph L, García-Alija M, Klontz E, Deredge D, Sultana N, Huynh CG, Flowers M, Li C, Sastre D, Wang LX, Corzana F, Mallagaray A, Sundberg EJ, Guerin ME*. Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases. Nat. Commun. 14(1):1705 (2023). doi: 10.1038/s41467-023-37215-3

  1. Cioetto-Mazzabò L, Boldrin F, Beauvineau C, Marina A, Speth M, Namouchi A, Cimino M, Favre-Rochex S, Segafreddo G, Balasingham S, Trastoy B, Munier-Lehmann H, Griffiths G, Gicquel B, Guerin ME, Manganelli R, Alonso-Rodríguez N. SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression. Nucl. Acids Res. 51(1):144-165 (2023). doi: 10.1093/nar/gkac1173

  1. Cordeiro RL, Santos CR, Domingues MN, Lima TB, Pirolla RAS, Morais MAB, Colombari FM, Miyamoto RY, Persinoti GF, Borges AC, Stoffel F, Li C, Gozzo FC, van Heel M, Guerin ME, Sundberg EJ, Wang L-X, Portugal RV, Giuseppe PO, Murakami MT. Mechanisms of high-mannose N-glycan breakdown and metabolism by the human gut commensal Bifidobacterium longum. Nat. Chem. Biol. 19(2):218-229 (2022). Highlighted in the News and Views section: A sweet feast. Crouch LI. 19(2):131-132. Nat. Chem. Biol. (2023). doi: 10.1038/s41589-022-01202-4

  1. García-Alija M, Du JJ, Ordóñez I, Diz-Vallenilla A, Moraleda-Montoya A, Sultana N, Huynh C, Li C, Donahue T, Wang L-X., Trastoy B, Sundberg EJ, Guerin ME*. Mechanism of cooperative N-glycan processing by the multi-modular endoglycosidase EndoE. Nat. Commun. 13:1137 (2022). doi: 10.1038/s41467-022-28722-w

  1. Trastoy B, Du JJ, García-Alija M, Li C, Klontz EH, Wang LX, Sundberg EJ, Guerin ME*. Sculpting N-glycosylation of therapeutic monoclonal antibodies by the use of specific endoglycosidases. Curr. Opin. Struct. Biol. 72:248-259. Highlighted as a Faculty Opinions article (2022). Review. doi: 10.1016/j.sbi.2021.11.016

  1. Anso I, Basso LGM, Wang L, Marina A, Páez-Pérez ED, Jäger C, Gavotto F, Tersa M, Perrone S, Contreras F.-X, Prandi J, Gilleron M, Linster CL, Corzana F, Lowary TL, Trastoy B, Guerin ME*. Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA. Sci. Adv. 7:eabj4565 (2021). doi: 10.1126/sciadv.abj4565

  1. Trastoy B, Du JJ, Li C, García-Alija M, Klontz EH, Roberts BR, Donahue TC, Wang LX, Sundberg EJ, Guerin ME*. GH18 endo-β-N-acetylglucosaminidases use distinct mechanisms to process hybrid-type N-linked glycans. J. Biol. Chem. 297:101011 (2021). doi: 10.1016/j.jbc.2021.101011

  1. Boldrin F, Anso I, Alebouyeh S, Sevilla IA, Geijo M, Garrido JM, Marina A, Cioetto Mazzabò L, Segafreddo G, Guerin ME, Manganelli R, Prados-Rosales R. The phosphatidyl-myo-inositol dimannoside acyltransferase PatA is essential for Mycobacterium tuberculosis growth in vitro and in vivo. J. Bacteriol. 203:e00439-20 (2021). doi: 10.1128/jb.00439-20

  1. Trastoy B, Anso I, Naegeli A, Sjögren J, Guerin ME*. Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila. Nat. Commun. 11:4844 (2020). doi: 10.1038/s41467-020-18696-y

  1. Liebau J, Tersa M, Trastoy B, Patrick J, Rodrigo-Unzueta A, Sparrman T, Guerin ME*, Mäler L. Unveiling the activation dynamics of a fold-switch bacterial glycosyltransferase by 19F NMR. J. Biol. Chem. 295:9868-9878 (2020). doi: 10.1074/jbc.RA120.014162

  1. Trastoy B, Du JJ, Klontz EH, Li C, Cifuente JO, Wang LX, Sundberg EJ, Guerin ME*. Structural basis of mammalian high-mannose N-glycans processing by human gut Bacteroides. Nat. Commun. 11:899 (2020). Highlighted as F1000Prime article (2020). doi: 10.1038/s41467-020-14754-7

  1. Rodrigo-Unzueta A, Ghirardello M, Urresti S, Delso I, Giganti D, Anso I, Trastoy B, Comino N, Tersa M, D’Angelo C, Cifuente JO, Marina A, Liebau J, Mäler L, Chenal A, Albesa-Jové D, Merino P, Guerin ME*. Dissecting the structural and chemical determinants of the ‘open-to-closed’ motion in the mannosyltransferase PimA from mycobacteria. Biochemistry 59(32): 2934-2945 (2020). doi: 10.1021/acs.biochem.0c00376

  1. Cifuente JO, Comino N, D’Angelo C, Marina A, Gil-Carton D, Albesa-Jové D, Guerin ME*. The allosteric control mechanism of bacterial glycogen biosynthesis disclosed by cryoEM. Curr. Res. Struct. Biol. 2:89-103 (2020). doi: 10.1016/j.crstbi.2020.04.005

  1. Sastre DM, Basso LGM, Trastoy B, Contreras X, Gueiros-Filho F, de Mendoza D, Navarro MVAS, Guerin ME*. Membrane fluidity adjusts the insertion and activity of the transacylase PlsX to regulate phospholipid biosynthesis in Gram positive bacteria. J. Biol. Chem. 295:2136-2147 (2020). Highlighted in the Lipid News section of ASBMB Today (2020). doi: 10.1074/jbc.ra119.011122

  1. Du JJ, Klontz EH, Guerin ME, Trastoy B, Sundberg EJ. Structural insights into the mechanisms and specificities of IgG-active endoglycosidases. Glycobiology 30(4):268-279 (2020). Review. doi: 10.1093/glycob/cwz042

  1. Grifoll-Romero L, Sainz-Polo MA, Albesa-Jové D, Guerin ME, Biarnés X, Planas A. Structure-function relationships underlying the dual N-acetylmuramic and N-acetylglucosamine specificities of the peptidoglycan deacetylase PdaC from Bacillus subtilis. J. Biol. Chem. 294(50):19066-19080 (2019). doi: 10.1074/jbc.ra119.009510

  1. Klontz, EH, Trastoy B, Deredge D, Fields JK, Orwenyo J, Beadenkopf R, Günther S, Flores J, Wintrode P, Wang LX, Guerin ME*, Sundberg EJ. Molecular basis of broad spectrum N-glycan specificity and processing of therapeutic IgG monoclonal antibodies by Endoglycosidase S2. ACS Cent. Sci. 5(3):524-538 (2019). Highlighted as F1000Prime article (2019). doi: 10.1021/acscentsci.8b00917

  1. Paczia N, Becker-Kettern J, Conrotte JF, Cifuente JO, Guerin ME, Linster CL. 3-Phosphoglycerate transhydrogenation instead of dehydrogenation alleviates redox state dependency of yeast de novo L-serine synthesis. Biochemistry 58(4):259-275 (2019). doi: 10.1021/acs.biochem.8b00990

  1. Cifuente JO, Comino N, Trastoy, B, D’Angelo C, Guerin ME*. Structural basis of glycogen metabolism in bacteria. Biochem. J. 476(14):2059-2092 (2019). Review. doi: 10.1042/bcj20170558

  1. Kalscheuer R, Palacios A, Anso I, Anguita J, Jacobs Jr. WR, Guerin ME, Prados-Rosales R. The Mycobacterium tuberculosis capsule: a cell structure with key implications in pathogenesis. Biochem. J. 476(14):1995-2016 (2019). Review. doi: 10.1042%2FBCJ20190324

  1. Albesa-Jové D, Cifuente JO, Trastoy B, Guerin ME*. Quick-soaking of crystals reveals unprecedented insights into the catalytic mechanism of glycosyltransferases. Methods Enzymol. 621:261-279 (2019). Review. doi: 10.1016/bs.mie.2019.02.034

  1. Cabrera Y, Dublanga L, Fernández-Higuero JA, Albesa-Jové D, Lucas M, Viguera AR, Guerin ME, Vilar JMG, Muga A, Moro F. Regulation of human Hsc70 ATPase and chaperone activities by Apg2: role of the acidic subdomain. J. Mol. Biol. 431(2):444-461 (2019). doi: 10.1016/j.jmb.2018.11.026

  1. Guerin ME, Stirnemann G, Giganti D. Conformational entropy of a single peptide controlled under force governs protease recognition and catalysis. Proc. Natl. Acad. Sci. USA 115(45):11525-11530 (2018). doi: 10.1073/pnas.1803872115

  1. Trastoy B, Klontz E, Orwenyo J, Marina A, Wang LX, Sundberg EJ, Guerin ME*. Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S. Nat. Commun. 9(1):1874 (2018). doi: 10.1038/s41467-018-04300-x

  1. Tersa T, Raich L, Albesa-Jové D, Trastoy B, Prandi J, Gilleron M, Rovira C, Guerin ME*. The molecular mechanism of substrate recognition and catalysis of the membrane acyltransferase PatA. ACS Chem. Biol. 13(1):131-140 (2018). doi: 10.1021/acschembio.7b00578

  1. Albesa-Jové D, Sainz-Polo MA, Marina A, Guerin ME*. Structural snapshots of the reaction center of α1,3-galactosyltransferase with native substrates support a conserved catalytic mechanism for retaining glycosyltransferases. Angew Chem Int Ed Engl. 56(47):14853-14857 (2017). doi: 10.1002/anie.201707922

  1. Rosado LA, Wahni K, De Giacomi G, Pedre B, Young D, de la Rubia AG, Boldrin F, Martens E, Marcos-Pascual L, Sancho-Vaello E, Albesa-Jové D, Provvedi R, Martin C, Makarov V, Versees W, Verniest G, Guerin ME, Mateos LM, Manganelli R, Messens J. The antibacterial prodrug activator Rv2466c is a mycothiol-dependent reductase in the oxidative stress response of Mycobacterium tuberculosis. J. Biol. Chem. 292(32):13097-13110 (2017). doi: 10.1074/jbc.m117.797837

  1. Albesa-Jové D, Romero-García J, Sancho-Vaello E, Contreras F-X, Rodrigo-Unzueta A, Comino N, Carreras-González A, Arrasate P, Urresti S, Biarnés X, Planas A, Guerin ME*. Structural snapshots and loop dynamics along the catalytic cycle of glycosyltransferase GpgS. Structure 25(7):1034-1044 (2017). doi: 10.1016/j.str.2017.05.009

  1. Comino N, Cifuente JO, Marina A, Orrantia A, Eguzquiza A, Guerin ME*. Mechanistic insights into the allosteric regulation of bacterial ADP-glucose pyrophosphorylases. J. Biol. Chem. 292(15):6255-6268 (2017). doi: 10.1074/jbc.m116.773408

  1. Sancho-Vaello E, Albesa-Jové D, Rodrigo-Unzueta A, Guerin ME*. Structural basis of phosphatidyl-myo-inositol mannosides biosynthesis in mycobacteria. Biochem. Biophys. Acta. 1862(11):1355-1367 (2017). Review. doi: 10.1016/j.bbalip.2016.11.002

  1. Cifuente JO, Comino N, Madariaga-Marcos J, López-Fernández S, Garcia-Alija M, Agirre J, Albesa-Jové, Guerin ME*. Structural basis of glycogen biosynthesis regulation in bacteria. Structure 24(9):1613-1622 (2016). doi: 10.1016/j.str.2016.06.023

  1. Albesa-Jové D, Guerin ME*. The conformational plasticity of glycosyltransferases. Curr. Opin. Struct. Biol. 40:23-32 (2016). Review. doi: 10.1016/j.sbi.2016.07.007

  1. Rodrigo-Unzueta A, Martínez MA, Comino N, Alzari PM, Chenal A, Guerin ME*. Molecular basis of membrane association by the phosphatidylinositol mannosyltransferase PimA from mycobacteria. J. Biol. Chem. 291(27):13955-13963 (2016). doi: 10.1074/jbc.m116.723676

  1. Albesa-Jové D, Svetlíková Z, Tersa M, Sancho-Vaello E, Carreras-González A, Bonnet P, Arrasate P, Angala SK, Cifuente JO, Korduláková J, Jackson M, Mikušová K, Guerin ME*. Structural basis for selective recognition of acyl chains by the integral membrane associated acyltransferase PatA. Nat. Commun. 7:10906 (2016). doi: 10.1038/ncomms10906

  1. Albesa-Jové D, Comino N, Tersa M, Mohorko E, Urresti S, Dainese E, Chiarelli LR, Pasca MR, Manganelli R, Makarov V, Riccardi G, Svergun I, Glockshuber R, Guerin ME*. The redox state regulates the conformation of Rv2466c to activate TP053 and kill Mycobacterium tuberculosis. J. Biol. Chem. 290(52):31077-31089 (2015). doi: 10.1074/jbc.m115.677039

  1. Albesa-Jové D, Mendoza F, Rodrigo-Unzueta A, Gomollón-Bel F, Cifuente JO, Urresti S, Comino N, Gómez H, Romero-García J, Lluch JM, Sancho-Vaello E, Biarnés X, Planas A, Merino P, Masgrau L Guerin ME*. A native ternary complex trapped in crystal reveals the catalytic mechanism of a retaining glycosyltransferase. Angew Chem Int Ed Engl. 54(34):9898-9902 (2015). doi: 10.1002/anie.201504617

  1. Giganti D, Albesa-Jové D, Urresti S, Rodrigo-Unzueta A, Martínez MA, Comino N, Barilone N, Bellinzoni M, Chenal A, Guerin ME*, Alzari PM. Secondary structure reshuffling modulates glycosyltransferase function at the membrane. Nat. Chem. Biol. 11(1):16-18 (2015). Highlighted in the News and Views section: Membrane enzymes: transformers at the interface. Brodhun F, Tittmann K. Nat. Chem. Biol. 11:102-103 (2015). doi: https://doi.org/10.1038/nchembio.1694

  1. Andrés E, Albesa-Jové D, Biarnés X, Moerschbacher BM, Guerin ME*, Planas A. Structural basis of chitin oligosaccharide deacetylation. Angew Chem Int Ed Engl. 53(27):6882-6887 (2014). doi: 10.1002/anie.201400220

  1. Albesa-Jové D, Chiarelli LR, Makarov V, Pasca MR, Urresti S, Mori G, Salina E, Vocat A, Comino N, Mohorko E, Ryabova S, Pfieiffer B, Lopes Ribeiro AL, Rodrigo-Unzueta A, Tersa M, Zanoni G, Buroni S, Altmann KH, Hartkoorn RC, Glockshuber R, Cole ST, Riccardi G, Guerin ME*. Rv2466c mediates the activation of TP053 to kill replicating and non-replicating Mycobacterium tuberculosis. ACS Chem. Biol. 9(7):1567-1575 (2014). Editor’s choice. doi: 10.1021/cb500149m

  1. Albesa-Jové D, Giganti D, Jackson M, Alzari PM, Guerin ME*. Structure-function relationships of membrane-associated GT-B glycosyltransferases. Glycobiology 24(2):108-124 (2014). Review. doi: 10.1093/glycob/cwt101

  1. Boldrin F, Ventura M, Degiacomi G, Ravishankar S, Sala C, Svetlikova Z, Ambady A, Dhar N, Kordulakova J, Zhang M, Serafini A, Vishwas KG, Kolly GS, Kumar N, Palù G, Guerin ME, Mikusova K, Cole ST, Manganelli R. The phosphatidyl-myo-inositol mannosyltransferase PimA is essential for Mycobacterium tuberculosis growth in vitro and in vivo. J. Bacteriol. 196(19):3441-3451 (2014). doi: 10.1128/jb.01346-13

  1. Giganti D, Alegre-Cebollada J, Urresti S, Albesa-Jove D, Rodrigo-Unzueta A, Comino N, Kachala M, Lopez-Fernandez S, Svergun DI, Fernandez JM, Guerin ME.* Conformational plasticity of the essential membrane associated mannosyltransferase PimA from mycobacteria. J. Biol. Chem. 288(41):29797-29808 (2013). doi: 10.1074/jbc.m113.462705

  1. Albanesi D, Reh G, Guerin ME, Schaeffer F, Debarbouille M, Buschiazzo A, Schujman G, de Mendoza D, Alzari PM. Structural basis for feed-forward transcriptional regulation of membrane lipid homeostasis in Staphylococcus aureus. PLoS Pathog. 9(1):e1003108 (2013). doi: 10.1371/journal.ppat.1003108

  1. Urresti S, Albesa-Jove D, Schaeffer F, Gest P, Pham HT, van der Woerd M, Carreras-Gonzalez A, Lopez-Fernandez S, Brennan PJ, Alzari PM, Jackson M, Guerin ME*. Mechanistic insights into the retaining glucosyl-3-phosphoglycerate synthase GpgS from Mycobacterium tuberculosis. J. Biol. Chem. 287(29):24649-24661 (2012). doi: 10.1074/jbc.M112.368191

  1. Santangelo MP, Gest PM, Guerin ME, Coincon M, Pham H, Ryan G, Puckett SE, Spencer JS, Gonzalez-Juarrero M, Daher R, Lenaerts AJ, Schnappinger D, Therisod M, Ehrt S, Sygusch J, Jackson M. Glycolytic and non-glycolytic functions of the fructose-1,6-bisphosphate aldolase of Mycobacterium tuberculosis, an essential enzyme produced by replicating and persistent bacilli. J. Biol. Chem. 286(46):40219-40231 (2011). doi: 10.1074/jbc.m111.259440

  1. Guerin ME*, Korduláková J, Alzari PM, Brennan PJ, Jackson M. Molecular basis of phosphatidylinositol mannosides biosynthesis and regulation in mycobacteria. J. Biol. Chem. 285(44):33577-33583 (2010). Review. doi: 10.1074/jbc.R110.168328

  1. Daher R, Coincon M, Fonvielle M, Gest P, Guerin ME, Jackson M, Sygusch J, Therisod M. Rational design, synthesis and evaluation of new selective inhibitors of microbial class II (zinc dependent) fructose bis-phosphate aldolases. J. Med. Chem. 53(21):7836-7842 (2010). doi: 10.1021%2Fjm1009814

  1. Guerin ME*, Kaur D, Somashekar BS, Gibbs S, Gest P, Chatterjee D, Brennan P, Jackson M. Insight into the molecular mechanism of the early steps of phosphatidylinositol mannosides biosynthesis in mycobacteria. J. Biol. Chem. 284(38):25687-25696 (2009). doi: 10.1074/jbc.M109.030593

  1. Guerin ME*, Schaeffer F, Chaffotte A, Gest P, Giganti D, Korduláková J, van der Woerd M, Jackson M, Alzari PM. Substrate-induced conformational changes in the essential peripheral-membrane binding mannosyltransferase PimA from mycobacteria. Implications for catalysis. J. Biol. Chem. 284(32):21613-21625 (2009). doi: 10.1074/jbc.M109.003947

  1. Kaur D, Pham HT, Larrouy-Maumus G, Riviere M, Vissa V, Guerin ME, Puzo G, Brennan PJ, Jackson M. Initiation of methylglucose lipopolysaccaride biosynthesis in mycobacteria. PLoS One 4(5):e5447 (2009). doi: 10.1371/journal.pone.0005447

  1. Kaur D, Guerin ME, Skovierová H, Brennan PJ, Jackson M. Biogenesis of glycoconjugates in Mycobacterium tuberculosis. Adv. Appl. Microbiol. 69:23-78 (2009). Review. doi: 10.1016%2FS0065-2164(09)69002-X

  1. Gest P, Kaur D, Pham HT, van der Woerd M, Hansen E, Brennan PJ, Jackson M, Guerin ME*. Preliminary crystallographic analysis of GpgS, a key glucosyltransferase involved in methylglucose lipopolysaccharides biosynthesis in Mycobacterium tuberculosis. Acta Cryst F64(12):1121-1124 (2008). doi: 10.1107/s1744309108032892

  1. Stadthagen G, Sambou T, Guerin ME, Barilone N, Boudou F, Korduláková J, Charles P, Alzari PM, Lemassu A, Daffé M, Puzo G, Gicquel B, Rivière M, Jackson M. Genetic bases for the biosynthesis of methylglucose lipopolysaccharides in Mycobacterium tuberculosis. J. Biol. Chem. 282(37):27270-27276 (2007). doi: 10.1074/jbc.m702676200

  1. Guerin ME, Korduláková J, Schaeffer F, Svetliková Z, Buschiazzo A, Giganti D, Gicquel B, Mikusová K, Jackson M, Alzari PM. Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria. J. Biol. Chem. 282(28):20705-20714 (2007). doi: 10.1074/jbc.m702087200

  1. Schujman GE*, Guerin ME*, Buschiazzo A, Schaeffer F, Llarrull L, Reh G, Vila AJ, Alzari PM, de Mendoza D. Structural basis of lipid biosynthesis regulation in Gram-positive bacteria. EMBO J. 25(17):4074-4083 (2006). * These authors contributed equally to this work. doi: 10.1038/sj.emboj.7601284

  1. Guerin ME, Buschiazzo A, Korduláková J, Jackson M, Alzari PM. Crystallization and preliminary crystallographic analysis of PimA, an essential mannosyltransferase from Mycobacterium smegmatis. Acta Cryst F61(5):518-520 (2005). doi: 10.1107/S1744309105012364

  1. Buschiazzo A, Ugalde JE, Guerin ME, Ugalde RA, Sheppard W, Alzari PM. Structure of glycogen synthase: homologous enzymes catalyze glycogen synthase and degradation. EMBO J. 23(16):3196-3205 (2004). Highlighted in the ESRF Highlights 2004. doi: 10.1038/sj.emboj.7600324

  1. Guerin ME, Buschiazzo A, Ugalde JE, Ugalde RA, Alzari PM. Preliminary crystallographic studies of the glycogen synthase from Agrobacterium tumefaciens. Acta Cryst D59(3):526-528 (2003). doi: 10.1107/S0907444902023119

  1. Guerin ME, Parodi, A.J. The UDP-glucose:glycoprotein glucosyltransferase is organized in at least two tightly bound domains from yeast to mammals. J. Biol. Chem. 278(23):20540-20546 (2003). doi: 10.1074/jbc.M300891200

  1. Pastini AC, Iglesias SR, Carricarte VC, Guerin ME, Sánchez DO, Frasch AC. Immunoassay with recombinant Trypanosoma cruzi antigens potentially useful for screening donated blood and diagnosing Chagas disease Clin. Chem. 40(10):1893-1897 (1994). doi: 10.1093/clinchem/40.10.1893

Project funding

  1. ELKARTEK grant No.: KK-2022/00107 (2022-2023)

Marine polysaccharide processing enzymes with biomedical and biotechnological impact.

Award: 760.545 euros. 168.359 euros to Prof. Guerin’ lab as Co-PI.

 

  1. R01 NIH grant No.: AI149297-01 (2019-2024)

Rationalizing glycoengineering strategies for immunotherapeutic antibodies.

Award: 2.961.611 US dollars. 334.260 US dollars to Prof. Guerin’ lab as Co-PI.

 

  1. MICINN grant No.: PID2019-105649RB-I00 (2020-2023)

Structural basis of glycan diversity

Award: 290.400 euros + FPI Fellow – a 4 years’ contract for a Ph.D. student.

Proyecto PID2019-105649RB-I00 financiado por:

 

  1. ELKARTEK grant No.: KK-2021-00034 (2021)

Marine polysaccharide hydrolyzing enzymes: biotechnological applications.

Award: 230.468 euros. 82.768 euros to Prof. Guerin’ lab as Co-PI.

 

  1. MINECO grant No.: SEV-2016-0644 (2017-2020)

Center of excellence Severo Ochoa – Institutional Grant. Role: Co-PI.

Award: 4.000.000 euros – Doctoral Fellow, a 4 years’ contract for a Ph.D. student – joint with LCSB Luxembourg.

 

  1. MINECO grant No.: BFU2017-92223-EXP (2019-2020)

Visualizing Enzymatic Transition States by Ultra-Fast X-ray Pulses

Award: 48.800 euros.

Proyecto BFU2017-92223-EXP financiado por:

 

  1. ELKARTEK grant No.: KK-2019-00076 (2019-2020)

Microbial Exopolysaccharides: diversity, functions and applications.

Award: 628.737 euros. 76.576 euros to Prof. Guerin’ lab as Co-PI.

 

  1. MINECO grant No.: BFU2016-77427-C2-2-R (2017-2019)

Substrate specificity and mechanisms of carbohydrate active enzymes: applications to biomedicine and biotechnology

Award: 217.800 euros + FPI Fellow, a 4 years’ contract for a Ph.D. student.

Proyecto BFU2016-77427-C2-2-R financiado por:

 

  1. European Commission FP7 grant No.: HEALTH-F3-2011-260872 (2011-2016)

More medicines for tuberculosis (MM4TB)

Award: 16.698.641 euros. 260.000 euros to Prof. Guerin’ lab as Co-PI.

 

  1. MINECO grant No.: BIO2013-4902-C2-2-R (2014-2017)

Understanding and engineering substrate specificity of carbohydrate active enzymes: implications in biomedical and biotechnological applications

Award: 108.900 euros.

 

  1. ETORTEK proyecto No.: IE14-385 (2014-2015)

Nanoglycotechnology: strategic research and technological development of biomedical applications.

Award: 108.486 euros to Prof. Guerin’ lab as Co-PI.

 

  1. European Commission FP6 grant No.: LSHP-CT-2005-018923 (2006-2010)

New medicines for tuberculosis (NM4TB)

Award: 50.000 euros.

 

  1. MINECO grant No.: SAF2010-19096 (2011-2013)

Targeting Mycobacterium tuberculosis through the inhibition of its essential phosphatidylinositol mannosyltransferase PimA

Award: 114.950 euros + FPI Fellow, a 4 years’ contract for a Ph.D. student.

Vacancies/Jobs

Applications from highly motivated, enthusiastic and hard-worker students/scientists are very welcome anytime. Please, send a brief letter with your CV, to Marcelo Guerin at mrccri@ibmb.csic.es

 

  1. Postdoctoral positions

Ramón y Cajal Fellowships MINECO – Spain.

Juan de la Cierva Fellowships MINECO – Spain.

Basque Government Fellowships – The Basque Country, Spain.

University of Barcelona Fellowships – The Basque Country, Spain.

La Caixa Foundation Junior Leader Fellowships – Spain. Two types: Incoming and Retaining.

EU Marie Curie Intra-European and International Incoming Fellowshipshttps://ec.europa.eu/research/mariecurieactions/

EMBO Fellowshipshttp://www.embo.org/funding-awards/fellowships

FEBS Fellowshipshttp://www.febs.org/our-activities/fellowships/

HFSP Fellowshipshttps://www.hfsp.org/funding/hfsp-funding/postdoctoral-fellowships

 

  1. Ph.D. studies

FPI Fellowships MINECO – Spain.

FPU Fellowships MINECO – Spain.

La Caixa Foundation – INPhINIT – Spain.

 

  1. Summer or Short Studentships / Internships

A two-four-months research project is usually available during the summer (e.g. June, July, August and/or September). Furthermore, we are happy to consider applications from highly motivated, enthusiastic and hard-worker students interested in carrying out internship or visiting research projects. Please contact me at mrccri@ibmb.csic.es if you are interested in exploring these opportunities.

Lab corner

You will find detailed information at https://sites.google.com/site/guerinlab/home

Contact

Marcelo Guerin

Research Professor

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