4kpg | pdb_00004kpg
Crystal structure of MycP1 from the ESX-1 type VII secretion system
Structural highlights
FunctionMYCP1_MYCS2 May play a dual role in regulation of ESX-1 secretion and virulence. Acts as a protease that cleaves EspB.[1] [2] Publication Abstract from PubMedMycobacteria use specialized type VII (ESX) secretion systems to export proteins across their complex cell walls. Mycobacterium tuberculosis encodes five nonredundant ESX secretion systems, with ESX-1 being particularly important to disease progression. All ESX loci encode extracellular membrane-bound proteases called mycosins (MycP) that are essential to secretion and have been shown to be involved in processing of type VII-exported proteins. Here, we report the first x-ray crystallographic structure of MycP1(24-407) to 1.86 A, defining a subtilisin-like fold with a unique N-terminal extension previously proposed to function as a propeptide for regulation of enzyme activity. The structure reveals that this N-terminal extension shows no structural similarity to previously characterized protease propeptides and instead wraps intimately around the catalytic domain where, tethered by a disulfide bond, it forms additional interactions with a unique extended loop that protrudes from the catalytic core. We also show MycP1 cleaves the ESX-1 secreted protein EspB from both M. tuberculosis and Mycobacterium smegmatis at a homologous cut site in vitro. Structure of the Mycosin-1 Protease from the Mycobacterial ESX-1 Protein Type VII Secretion System.,Solomonson M, Huesgen PF, Wasney GA, Watanabe N, Gruninger RJ, Prehna G, Overall CM, Strynadka NC J Biol Chem. 2013 Jun 14;288(24):17782-90. doi: 10.1074/jbc.M113.462036. Epub, 2013 Apr 25. PMID:23620593[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
