5C00

MdbA protein, a thiol-disulfide oxidoreductase from Corynebacterium diphtheriae


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.77 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.164 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.

Reardon-Robinson, M.E.Osipiuk, J.Jooya, N.Chang, C.Joachimiak, A.Das, A.Ton-That, H.

(2015) Mol Microbiol 98: 1037-1050

  • DOI: https://doi.org/10.1111/mmi.13172
  • Primary Citation of Related Structures:  
    5C00

  • PubMed Abstract: 

    The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae.


  • Organizational Affiliation

    Department of Microbiology & Molecular Genetics, University of Texas Health Science Center, Houston, TX, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MdbA protein
A, B, C, D
208Corynebacterium diphtheriae NCTC 13129Mutation(s): 0 
Gene Names: DIP1880
UniProt
Find proteins for Q6NFK7 (Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis))
Explore Q6NFK7 
Go to UniProtKB:  Q6NFK7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6NFK7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B, C, D
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.77 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.164 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 61.532α = 90
b = 76.621β = 90.17
c = 72.586γ = 90
Software Package:
Software NamePurpose
HKL-3000data scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-3000data reduction
HKL-3000phasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)United StatesDE025015

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-15
    Type: Initial release
  • Version 1.1: 2015-09-09
    Changes: Database references
  • Version 1.2: 2016-01-27
    Changes: Database references
  • Version 1.3: 2017-09-27
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.4: 2019-12-11
    Changes: Author supporting evidence