An analysis of 60 metallopeptidase zymogens 3D structures revealed that their latency mechanism is less conserved than catalysis one.

The Proteolysis laboratory, directed by F. X. Gomis-Rüth, published a review about the latency of metallopeptidase zymogens at Chemical Reviews Journal, one of the most highly regarded and highest-ranked journals covering the general topic of chemistry.

This revision focuses on the structural determinants of inhibition in zymogens of metallopeptidases (MPs). These enzymes cleave polypeptides bound in the active-site cleft of catalytic domains through a general base/acid mechanism. This involves a solvent molecule bound to a catalytic zinc and general regulation of the mechanism through zymogen-based latency. Sixty reported structures from 11 metallopeptidase families reveal that prosegments, mostly N-terminal of the catalytic domain, block the cleft regardless of their size. Prosegments may be peptides (5−14 residues), which are only structured within the zymogens, or large moieties (<227 residues) of one or two folded domains. While some prosegments globally shield the catalytic domain through a few contacts, others specifically run across the cleft in the same or opposite direction as a substrate, making numerous interactions. Some prosegments block the zinc by replacing
the solvent with particular side chains, while others use terminal α-amino or carboxylate groups. Overall, metallopeptidase zymogens employ disparate mechanisms that diverge even within families, which supports that latency is less conserved than catalysis.