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PDBsum entry 4mcu
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Oxidoreductase
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PDB id
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4mcu
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PDB id:
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| Name: |
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Oxidoreductase
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Title:
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Crystal structure of disulfide oxidoreductase from klebsiella pneumoniae in reduced state
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Structure:
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Thiol:disulfide interchange protein. Chain: a, b, c, d, e, f. Engineered: yes
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Source:
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Klebsiella pneumoniae. Organism_taxid: 507522. Strain: 342. Gene: dsba, kpk_5512. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.99Å
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R-factor:
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0.168
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R-free:
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0.196
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Authors:
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F.Kurth,L.Premkumar,J.L.Martin
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Key ref:
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F.Kurth
et al.
(2013).
Comparative sequence, structure and redox analyses of Klebsiella pneumoniae DsbA show that anti-virulence target DsbA enzymes fall into distinct classes.
Plos One,
8,
e80210.
PubMed id:
DOI:
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Date:
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21-Aug-13
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Release date:
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27-Nov-13
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PROCHECK
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Headers
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References
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B5XZJ6
(B5XZJ6_KLEP3) -
Thiol:disulfide interchange protein from Klebsiella pneumoniae (strain 342)
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Seq:
Struc:
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207 a.a.
188 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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DOI no:
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Plos One
8:e80210
(2013)
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PubMed id:
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Comparative sequence, structure and redox analyses of Klebsiella pneumoniae DsbA show that anti-virulence target DsbA enzymes fall into distinct classes.
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F.Kurth,
K.Rimmer,
L.Premkumar,
B.Mohanty,
W.Duprez,
M.A.Halili,
S.R.Shouldice,
B.Heras,
D.P.Fairlie,
M.J.Scanlon,
J.L.Martin.
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ABSTRACT
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Bacterial DsbA enzymes catalyze oxidative folding of virulence factors, and have
been identified as targets for antivirulence drugs. However, DsbA enzymes
characterized to date exhibit a wide spectrum of redox properties and divergent
structural features compared to the prototypical DsbA enzyme of Escherichia coli
DsbA (EcDsbA). Nonetheless, sequence analysis shows that DsbAs are more highly
conserved than their known substrate virulence factors, highlighting the
potential to inhibit virulence across a range of organisms by targeting DsbA.
For example, Salmonella enterica typhimurium (SeDsbA, 86 % sequence identity to
EcDsbA) shares almost identical structural, surface and redox properties. Using
comparative sequence and structure analysis we predicted that five other
bacterial DsbAs would share these properties. To confirm this, we characterized
Klebsiella pneumoniae DsbA (KpDsbA, 81 % identity to EcDsbA). As expected, the
redox properties, structure and surface features (from crystal and NMR data) of
KpDsbA were almost identical to those of EcDsbA and SeDsbA. Moreover, KpDsbA and
EcDsbA bind peptides derived from their respective DsbBs with almost equal
affinity, supporting the notion that compounds designed to inhibit EcDsbA will
also inhibit KpDsbA. Taken together, our data show that DsbAs fall into
different classes; that DsbAs within a class may be predicted by sequence
analysis of binding loops; that DsbAs within a class are able to complement one
another in vivo and that compounds designed to inhibit EcDsbA are likely to
inhibit DsbAs within the same class.
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