Structure and Function of the Oxidoreductase DsbA1 from Neisseria meningitidis
| Autor: | Martin J. Scanlon, Bimbil Graham, Tristan Paul Boyle, Kieran Rimmer, Emma Byres, Begoña Heras, Matthew Charles James Wilce, Jamie S. Simpson, Charlene M. Kahler, Bradley C. Doak, Jamie Rossjohn, Julian P. Vivian, Travis Clarke Beddoe, Jessica Scoullar, S.R. Bushell |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Molecular Sequence Data Protein Disulfide-Isomerases Protein Data Bank (RCSB PDB) Sequence alignment Neisseria meningitidis Crystallography X-Ray Protein structure Structural Biology Oxidoreductase Catalytic Domain Amino Acid Sequence Molecular Biology chemistry.chemical_classification biology Escherichia coli Proteins Oxidative folding Active site Protein Structure Tertiary DsbA Biochemistry chemistry biology.protein Thioredoxin Oxidation-Reduction Sequence Alignment Protein Binding |
| Zdroj: | Journal of Molecular Biology. 394:931-943 |
| ISSN: | 0022-2836 |
| DOI: | 10.1016/j.jmb.2009.09.065 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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