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PDBsum entry 1acv
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Disulfide oxidoreductase
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PDB id
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1acv
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural analysis of three his32 mutants of dsba: support for an electrostatic role of his32 in dsba stability.
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Authors
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L.W.Guddat,
J.C.Bardwell,
R.Glockshuber,
M.Huber-Wunderlich,
T.Zander,
J.L.Martin.
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Ref.
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Protein Sci, 1997,
6,
1893-1900.
[DOI no: ]
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PubMed id
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Abstract
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DsbA, a 21-kDa protein from Escherichia coli, is a potent oxidizing disulfide
catalyst required for disulfide bond formation in secreted proteins. The active
site of DsbA is similar to that of mammalian protein disulfide isomerases, and
includes a reversible disulfide bond formed from cysteines separated by two
residues (Cys30-Pro31-His32-Cys33). Unlike most protein disulfides, the
active-site disulfide of DsbA is highly reactive and the oxidized form of DsbA
is much less stable than the reduced form at physiological pH. His32, one of the
two residues between the active-site cysteines, is critical to the oxidizing
power of DsbA and to the relative instability of the protein in the oxidized
form. Mutation of this single residue to tyrosine, serine, or leucine results in
a significant increase in stability (of approximately 5-7 kcal/mol) of the
oxidized His32 variants relative to the oxidized wild-type protein. Despite the
dramatic changes in stability, the structures of all three oxidized DsbA His32
variants are very similar to the wild-type oxidized structure, including
conservation of solvent atoms near the active-site residue, Cys30. These results
show that the His32 residue does not exert a conformational effect on the
structure of DsbA. The destabilizing effect of His32 on oxidized DsbA is
therefore most likely electrostatic in nature.
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Secondary reference #1
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Title
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The uncharged surface features surrounding the active site of escherichia coli dsba are conserved and are implicated in peptide binding.
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Authors
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L.W.Guddat,
J.C.Bardwell,
T.Zander,
J.L.Martin.
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Ref.
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Protein Sci, 1997,
6,
1148-1156.
[DOI no: ]
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PubMed id
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Figure 1.
Fig. 1. Stereo view of the structure of oxidized wt E. coli DsbA (from monomer A in the asyrnmetnc unit). Thisfigure was prepared
with the program MOLSCRIPT (Kraulis, 1991).
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Figure 5.
Fig. 5. The proosed peptide interaction surface ofDsbA.Left:Amodelof
theinteractionbetweenpeptide substrate andDsbA,basedonthehuman
thioredoxin:Ref-1peptidecomplex[(Qin et al., 1996b) DB accession
code lCQG]. The electrostatic surface ofDsbAisshown[generatedusing
GRASP (Nicholls et al., 1993)] withthe peptide n the thioredoxin-bound
conformation superimposed. The positionof the accessible sulfur of the
active-site disulfide is denoted by S.'' Right: CPKmodelofDsbA,show-
ing uncharged inyellow. Residues ithat least one
occurrence ofacharged amino acid (Asp, Glu, Lys, or kg) inthenine
aligned sequences are showninwhite. The conserved active-site cysteines
are shownin green.
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The above figures are
reproduced from the cited reference
which is an Open Access publication published by the Protein Society
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Secondary reference #2
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Title
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Crystal structure of the dsba protein required for disulphide bond formation in vivo.
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Authors
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J.L.Martin,
J.C.Bardwell,
J.Kuriyan.
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Ref.
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Nature, 1993,
365,
464-468.
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PubMed id
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