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PDBsum entry 1u3a
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Oxidoreductase
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PDB id
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1u3a
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References listed in PDB file
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Key reference
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Title
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Intriguing conformation changes associated with the trans/cis isomerization of a prolyl residue in the active site of the dsba c33a mutant.
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Authors
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E.Ondo-Mbele,
C.Vivès,
A.Koné,
L.Serre.
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Ref.
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J Mol Biol, 2005,
347,
555-563.
[DOI no: ]
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PubMed id
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Abstract
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Escherichia coli DsbA belongs to the thioredoxin family and catalyzes the
formation of disulfide bonds during the folding of proteins in the bacterial
periplasm. It active site (C30-P31-H32-C33) consists of a disulfide bridge that
is transferred to newly translocated proteins. The work reported here refers to
the DsbA mutant termed C33A that retains, towards reduced unfolded thrombin
inhibitor, an activity comparable with the wild-type enzyme. Besides, C33A is
also able to form a stable covalent complex with DsbB, the membrane protein
responsible for maintaining DsbA in its active form. We have determined the
crystal structure of C33A at 2.0 angstroms resolution. Although the general
architecture of wt DsbA is conserved, we observe the trans/cis isomerization of
P31 in the active site and further conformational changes in the so-called
"peptide binding groove" region. Interestingly, these modifications
involve residues that are specific to DsbA but not to the thioredoxin family
fold. The C33A crystal structure exhibits as well a hydrophobic ligand bound
close to the active site of the enzyme. The structural analysis of C33A may
actually explain the peculiar behavior of this mutant in regards with its
interaction with DsbB and thus provides new insights for understanding the
catalytic cycle of DsbA.
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Figure 1.
Figure 1. Ribbon representation of the C33A dimers. C30 and
A33 are represented by green ball-and-stick. (a) (Form Ia)
crystal structure containing dodecyl-maltoside (DDM) (in magenta
ball-and-stick). (b) (Form II) crystal structure containing PEG
(in magenta ball-and-stick). All Figures have been generated
with Molscript26 and Pymol (DeLano. http://www.pymol.org).
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Figure 4.
Figure 4. Structural rearrangement of V39, F36 and F93
around the ligand. DDM (green) or PEG (magenta) overlap with F36
residue in the wt enzyme structures (reduced and oxidized in
gray). The same residues in C33A are painted in yellow.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2005,
347,
555-563)
copyright 2005.
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