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The multidrug resistance IncA/C transferable plasmid encodes a novel domain swapped dimeric disulfide isomerase (976.1)
Author(s) -
Kurth Fabian,
Lakshmanane Premkumar,
Neyer Simon,
Schembri Mark,
Martin Jennifer
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.976.1
Subject(s) - isomerase , protein disulfide isomerase , plasmid , escherichia coli , biochemistry , structural genomics , linker , chemistry , oxidative folding , enzyme , biology , gene , protein structure , computational biology , computer science , operating system
The multidrug resistance‐encoding IncA/C conjugative plasmids disseminate antibiotic resistance genes among clinically relevant enteric bacteria. DsbP, a plasmid encoded disulfide isomerase is crucial for conjugation. The crystal structure of DsbP revealed a unique V shaped homodimer that is inverted with respect to known disulfide isomerases from E. coli (DsbC and DsbG). Dimer formation is mediated by an N‐terminal domain that includes a novel domain‐swapped interaction. Overall, the structure, surface and catalytic properties of DsbP diverge from those of Escherichia coli DsbC and DsbG disulfide isomerases. Functional 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 revealed conformational changes in the linker region, which 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. Grant Funding Source : Supported by an Australian Research Council (ARC) Australian Laureate Fellowship (FL0992138) to JLM