Document Detail


Structure and function of the oxidoreductase DsbA1 from Neisseria meningitidis.
MedLine Citation:
PMID:  19815019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-A-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.
Authors:
Julian P Vivian; Jessica Scoullar; Kieran Rimmer; Simon R Bushell; Travis Beddoe; Matthew C J Wilce; Emma Byres; Tristan P Boyle; Bradley Doak; Jamie S Simpson; Bim Graham; Bego??a Heras; Charlene M Kahler; Jamie Rossjohn; Martin J Scanlon
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-06
Journal Detail:
Title:  Journal of molecular biology     Volume:  394     ISSN:  1089-8638     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2009-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  931-43     Citation Subset:  IM    
Affiliation:
The Protein Crystallography Unit, Australian Research Council Center of Excellence in Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
Data Bank Information
Bank Name/Acc. No.:
PDB/3A3T
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Catalytic Domain
Crystallography, X-Ray
Escherichia coli Proteins / chemistry
Models, Molecular
Molecular Sequence Data
Neisseria meningitidis / enzymology*
Oxidation-Reduction
Protein Binding
Protein Disulfide-Isomerases / chemistry*,  metabolism*
Protein Structure, Tertiary
Sequence Alignment
Chemical
Reg. No./Substance:
0/Escherichia coli Proteins; EC 5.3.4.1/Protein Disulfide-Isomerases; EC 5.3.4.1/dsbA protein, E coli

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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