4KG7

Structure of MycP3 protease from the type VII (ESX-3) secretion system.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.153 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Understanding specificity of the mycosin proteases in ESX/type VII secretion by structural and functional analysis.

Wagner, J.M.Evans, T.J.Chen, J.Zhu, H.Houben, E.N.Bitter, W.Korotkov, K.V.

(2013) J Struct Biol 184: 115-128

  • DOI: https://doi.org/10.1016/j.jsb.2013.09.022
  • Primary Citation of Related Structures:  
    4HVL, 4KG7

  • PubMed Abstract: 

    Mycobacteria use specialized ESX secretion systems to transport proteins across their cell membranes in order to manipulate their environment. In pathogenic Mycobacterium tuberculosis there are five paralogous ESX secretion systems, named ESX-1 through ESX-5. Each system includes a subtilisin-like protease (mycosin or MycP) as a core component essential for secretion. Here we report crystal structures of MycP1 and MycP3, the mycosins expressed by the ESX-1 and ESX-3 systems, respectively. In both mycosins the putative propeptide wraps around the catalytic domain and does not occlude the active site. The extensive contacts between the putative propeptide and catalytic domain, which include a disulfide bond, suggest that the N-terminal extension is an integral part of the active mycosin. The catalytic residues of MycP1 and MycP3 are located in a deep active site groove in contrast with an exposed active site in majority of subtilisins. We show that MycP1 specifically cleaves ESX-1 secretion-associated protein B (EspB) in vitro at residues Ala358 and Ala386. We also systematically characterize the specificity of MycP1 using peptide libraries, and show that it has evolved a narrow specificity relative to other subtilisins. Finally, comparison of the MycP1 and MycP3 structures suggest that both enzymes have stringent and different specificity profiles that result from the structurally distinct active site pockets, which could explain the system specific functioning of these proteases.


  • Organizational Affiliation

    Department of Molecular & Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidase S8 and S53, subtilisin, kexin, sedolisin381Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: MSMEG_0624MSMEI_0608MycP3
UniProt
Find proteins for A0QQ47 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0QQ47 
Go to UniProtKB:  A0QQ47
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0QQ47
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CL
Query on CL

Download Ideal Coordinates CCD File 
B [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.153 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.82α = 77.27
b = 46.95β = 68.35
c = 47.54γ = 74.47
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
SERGUIdata collection
XDSdata reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-06-19
    Type: Initial release
  • Version 1.1: 2013-10-23
    Changes: Database references
  • Version 1.2: 2013-11-27
    Changes: Database references
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description