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Structural and biochemical characterisation of the oxidoreductase NmDsbA3 from Neisseria meningitidis

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journal contribution
posted on 2008-11-21, 00:00 authored by J Vivian, J Scoullar, A Robertson, S Bottomley, J Horne, Y Chin, J Wielens, P Thompson, Tony Velkov, S Piek, E Byres, T Beddoe, M Wilce, C Kahler, J Rossjohn, M Scanlon
DsbA is an enzyme found in the periplasm of Gram-negative bacteria that catalyses the formation of disulfide bonds in a diverse array of protein substrates, many of which are involved in bacterial pathogenesis. Whilst 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, whilst 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 reoxidised 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.

History

Journal

Journal of biological chemistry

Volume

283

Pagination

32452 - 32461

Location

Baltimore, Md.

Open access

  • Yes

ISSN

0021-9258

eISSN

1083-351X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal; C Journal article

Copyright notice

2008, The American Society for Biochemistry and Molecular Biology

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