4ML6

Disulfide isomerase from multidrug resistance IncA/C conjugative plasmid in reduced state

Summary for 4ML6

• Entry DOI: 10.2210/pdb4ml6/pdb
• Related: 4ML1 4MLY
• Descriptor: DsbP (2 entities in total)
• Functional Keywords: dsbc, dsbg, folding and assembly, bacterial conjugation, horizontal gene transfer, domain swapping, thioredoxin fold, bacterial periplasmic space, isomerase
• Biological source: Klebsiella pneumoniae
• Cellular location: Periplasm : A6GV51
• Total number of polymer chains: 4
• Total formula weight: 95689.76

Authors

Premkumar, L.,Kurth, F.,Neyer, S.,Martin, J.L. (deposition date: 2013-09-06, release date: 2013-12-11, Last modification date: 2024-10-16)

Primary citation

Premkumar, L.,Kurth, F.,Neyer, S.,Schembri, M.A.,Martin, J.L.
The Multidrug Resistance IncA/C Transferable Plasmid Encodes a Novel Domain-swapped Dimeric Protein-disulfide Isomerase.
J.Biol.Chem., 289:2563-2576, 2014

PubMed Abstract: The multidrug resistance-encoding IncA/C conjugative plasmids disseminate antibiotic resistance genes among clinically relevant enteric bacteria. A plasmid-encoded disulfide isomerase is associated with conjugation. Sequence analysis of several IncA/C plasmids and IncA/C-related integrative and conjugative elements (ICE) from commensal and pathogenic bacteria identified a conserved DsbC/DsbG homolog (DsbP). The crystal structure of DsbP reveals an N-terminal domain, a linker region, and a C-terminal catalytic domain. A DsbP homodimer is formed through domain swapping of two DsbP N-terminal domains. The catalytic domain incorporates a thioredoxin-fold with characteristic CXXC and cis-Pro motifs. Overall, the structure and redox properties of DsbP diverge from the Escherichia coli DsbC and DsbG disulfide isomerases. Specifically, the V-shaped dimer of DsbP is inverted compared with EcDsbC and EcDsbG. In addition, the redox potential of DsbP (-161 mV) is more reducing than EcDsbC (-130 mV) and EcDsbG (-126 mV). Other catalytic properties of DsbP more closely resemble those of EcDsbG than EcDsbC. These catalytic differences are in part a consequence of the unusual active site motif of DsbP (CAVC); substitution to the EcDsbC-like (CGYC) motif converts the catalytic properties to those of EcDsbC. Structural comparison of the 12 independent subunit structures of DsbP that we determined revealed that conformational changes in the linker region contribute to mobility of the catalytic domain, providing mechanistic insight into DsbP function. In summary, our data reveal that the conserved plasmid-encoded DsbP protein is a bona fide disulfide isomerase and suggest that a dedicated oxidative folding enzyme is important for conjugative plasmid transfer.

PubMed: 24311786
DOI: 10.1074/jbc.M113.516898

Experimental method

X-RAY DIFFRACTION (2.3 Å)