5VYO

The complex structure of Burkholderia pseudomallei DsbA bound to a peptide

Summary for 5VYO

• Entry DOI: 10.2210/pdb5vyo/pdb
• Descriptor: Thiol:disulfide interchange protein, Disulfide bond formation protein B (3 entities in total)
• Functional Keywords: thioredoxin, oxidoreductase, complex
• Biological source: Burkholderia pseudomallei; More
• Total number of polymer chains: 8
• Total formula weight: 90426.94

Authors

McMahon, R.M.,Martin, J.L. (deposition date: 2017-05-25, release date: 2018-03-21, Last modification date: 2024-11-20)

Primary citation

McMahon, R.M.,Ireland, P.M.,Sarovich, D.S.,Petit, G.,Jenkins, C.H.,Sarkar-Tyson, M.,Currie, B.J.,Martin, J.L.
Virulence of the Melioidosis Pathogen Burkholderia pseudomallei Requires the Oxidoreductase Membrane Protein DsbB.
Infect. Immun., 86:-, 2018

PubMed Abstract: The naturally antibiotic-resistant bacterium is the causative agent of melioidosis, a disease with stubbornly high mortality and a complex, protracted treatment regimen. The worldwide incidence of melioidosis is likely grossly underreported, though it is known to be highly endemic in northern Australia and Southeast Asia. Bacterial disulfide bond (DSB) proteins catalyze the oxidative folding and isomerization of disulfide bonds in substrate proteins. In the present study, we demonstrate that membrane protein disulfide bond protein B (BpsDsbB) forms a functional redox relay with the previously characterized virulence mediator disulfide bond protein A (BpsDsbA). Genomic analysis of diverse clinical isolates demonstrated that is a highly conserved core gene. Critically, we show that DsbB is required for virulence in A panel of deletion strains (K96243, 576, MSHR2511, MSHR0305b, and MSHR5858) were phenotypically diverse according to the results of assays that assess hallmarks of virulence. Irrespective of their virulence phenotypes, two deletion strains were attenuated in a BALB/c mouse model of infection. A crystal structure of a DsbB-derived peptide complexed with BpsDsbA provides the first molecular characterization of their interaction. This work contributes to our broader understanding of DSB redox biology and will support the design of antimicrobial drugs active against this important family of bacterial virulence targets.

PubMed: 29440370
DOI: 10.1128/IAI.00938-17

Experimental method

X-RAY DIFFRACTION (2.49 Å)