DsbA is an enzyme found in the periplasm of Gram-negative bacteria that catalyzes the formation of disulfide bonds in a diverse array of protein substrates, many of which are involved in bacterial pathogenesis. Although most bacteria possess only a single essential DsbA, Neisseria meningitidis is unusual in that it possesses three DsbAs, although the reason for this additional redundancy is unclear. Two of these N. meningitidis enzymes (NmDsbA1 and NmDsbA2) play an important role in meningococcal attachment to human epithelial cells, whereas NmDsbA3 is considered to have a narrow substrate repertoire. To begin to address the role of DsbAs in the pathogenesis of N. meningitidis, we have determined the structure of NmDsbA3 to 2.3-Å resolution. Although the sequence identity between NmDsbA3 and other DsbAs is low, the NmDsbA3 structure adopted a DsbA-like fold. Consistent with this finding, we demonstrated that NmDsbA3 acts as a thiol-disulfide oxidoreductase in vitro and is reoxidized by Escherichia coli DsbB (EcDsbB). However, pronounced differences in the structures between DsbA3 and EcDsbA, which are clustered around the active site of the enzyme, suggested a structural basis for the unusual substrate specificity that is observed for NmDsbA3.

Item Type:	Refereed Article
Keywords:	DsbA oxidoreductase specificity structure
Research Division:	Biological Sciences
Research Group:	Biochemistry and Cell Biology
Research Field:	Structural Biology (incl. Macromolecular Modelling)
Objective Division:	Expanding Knowledge
Objective Group:	Expanding Knowledge
Objective Field:	Expanding Knowledge in the Biological Sciences
UTAS Author:	Horne, HJ (Dr James Horne)
ID Code:	53316
Year Published:	2008
Web of Science® Times Cited:	20
Deposited By:	Central Science Laboratory
Deposited On:	2008-11-25
Last Modified:	2008-11-25
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