Mirolysin structures open a window on gum disease.

Evette S Radisky

doi:10.1107/s2052252519016968

Abstract

Guevara, Rodriguez-Banqueri et al. [(2020), IUCrJ, 7, 18-29] determine crystal structures of mirolysin, a metalloprotease that helps oral pathogen Tannerella forsythia evade the human immune response. The structures provide insight into the regulation and specificity of mirolysin, and hint at how it might be inhibited for therapeutic effect.

Highlights

In this issue of IUCrJ, Guevara, Rodriguez-Banqueri et al report high-resolution crystal structures of promirolysin, defining the mechanism of latency of the precursor protein (Guevara et al, 2020)
Mirolysin is first produced as a zymogen, maintained in an inactive state by the presence of an N-terminal extension known as a pro-peptide, pro-segment or pro-domain (Fig. 1)
The group finds that the mechanism of latency of promirolysin closely resembles the cysteine switch mechanism of matrix metalloproteinases (MMPs) and a number of other zinc metallopeptidases (Morgunova et al, 1999; Arolas et al, 2018)

Summary

Introduction

In this issue of IUCrJ, Guevara, Rodriguez-Banqueri et al report high-resolution crystal structures of promirolysin, defining the mechanism of latency of the precursor protein (Guevara et al, 2020). Mirolysin is first produced as a zymogen, maintained in an inactive state by the presence of an N-terminal extension known as a pro-peptide, pro-segment or pro-domain (Fig. 1). Upon proteolytic cleavage of the pro-segment, the active site of a protease becomes exposed and accessible to substrates.

Results

Conclusion