Structure and Function of the Oxidoreductase DsbA1 from Neisseria meningitidis

Vivian, J. P., Scoullar, J, Rimmer, K, Bushell, S. R., Beddoe, T, Wilce, M. C. J., Byres, E, Boyle, T. P., Doak, B, Simpson, J. S., Graham, B, Heras, B, Kahler, C. M., Rossjohn, J and Scanlon, M. J. (2009) Structure and Function of the Oxidoreductase DsbA1 from Neisseria meningitidis. Journal of Molecular Biology, 394 5: 931-943. doi:10.1016/j.jmb.2009.09.065

Author Vivian, J. P.
Scoullar, J
Rimmer, K
Bushell, S. R.
Beddoe, T
Wilce, M. C. J.
Byres, E
Boyle, T. P.
Doak, B
Simpson, J. S.
Graham, B
Heras, B
Kahler, C. M.
Rossjohn, J
Scanlon, M. J.
Title Structure and Function of the Oxidoreductase DsbA1 from Neisseria meningitidis
Formatted title
Structure and Function of the Oxidoreductase DsbA1 from Neisseria meningitidis
Journal name Journal of Molecular Biology   Check publisher's open access policy
ISSN 0022-2836
Publication date 2009-12
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.jmb.2009.09.065
Volume 394
Issue 5
Start page 931
End page 943
Total pages 13
Editor R. Huber
Place of publication London, United Kingdom
Publisher Academic Press (Elsevier Inc)
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060112 Structural Biology (incl. Macromolecular Modelling)
Formatted abstract
Neisseria meningitidis encodes three DsbA oxidoreductases (NmDsbA1–NmDsbA3) that are vital for the oxidative folding of many membrane and secreted proteins, and these three enzymes are considered to exhibit different substrate specificities. This has led to the suggestion that each N. meningitidis DsbA (NmDsbA) may play a specialized role in different stages of pathogenesis; however, the molecular and structural bases of the different roles of NmDsbAs are unclear. With the aim of determining the molecular basis for substrate specificity and how this correlates to pathogenesis, we undertook a biochemical and structural characterization of the three NmDsbAs. We report the 2.0-Å-resolution crystal structure of the oxidized form of NmDsbA1, which adopted a canonical DsbA fold similar to that observed in the structures of NmDsbA3 and Escherichia coli DsbA (EcDsbA). Structural comparisons revealed variations around the active site and candidate peptide-binding region. Additionally, we demonstrate that all three NmDsbAs are strong oxidases with similar redox potentials; however, they differ from EcDsbA in their ability to be reoxidized by E. coli DsbB. Collectively, our studies suggest that the small structural differences between the NmDsbA enzymes and EcDsbA are functionally significant and are the likely determinants of substrate specificity.
Keyword DsbAs
disulfide bonds
crystal structure
bacterial pathogen
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Available online 6 October 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 19 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 10 Jan 2010, 00:04:23 EST