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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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periplasmic space
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1 term
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Biological process
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response to antibiotic
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2 terms
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Biochemical function
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hydrolase activity
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4 terms
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DOI no:
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Antimicrob Agents Chemother
51:2136-2142
(2007)
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PubMed id:
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Competitive inhibitors of the CphA metallo-beta-lactamase from Aeromonas hydrophila.
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L.E.Horsfall,
G.Garau,
B.M.Liénard,
O.Dideberg,
C.J.Schofield,
J.M.Frère,
M.Galleni.
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ABSTRACT
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Various inhibitors of metallo-beta-lactamases have been reported; however, none
are effective for all subgroups. Those that have been found to inhibit the
enzymes of subclass B2 (catalytically active with one zinc) either contain a
thiol (and show less inhibition towards this subgroup than towards the dizinc
members of B1 and B3) or are inactivators behaving as substrates for the dizinc
family members. The present work reveals that certain pyridine carboxylates are
competitive inhibitors of CphA, a subclass B2 enzyme. X-ray crystallographic
analyses demonstrate that pyridine-2,4-dicarboxylic acid chelates the zinc ion
in a bidentate manner within the active site. Salts of these compounds are
already available and undergoing biomedical testing for various nonrelated
purposes. Pyridine carboxylates appear to be useful templates for the
development of more-complex, selective, nontoxic inhibitors of subclass B2
metallo-beta-lactamases.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.L.Stamp,
P.Owen,
K.E.Omari,
C.E.Nichols,
M.Lockyer,
H.K.Lamb,
I.G.Charles,
A.R.Hawkins,
and
D.K.Stammers
(2010).
Structural and functional characterization of Salmonella enterica serovar Typhimurium YcbL: an unusual Type II glyoxalase.
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Protein Sci, 19,
1897-1905.
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PDB code:
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C.Bebrone,
P.Lassaux,
L.Vercheval,
J.S.Sohier,
A.Jehaes,
E.Sauvage,
and
M.Galleni
(2010).
Current challenges in antimicrobial chemotherapy: focus on ß-lactamase inhibition.
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Drugs, 70,
651-679.
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P.Oelschlaeger,
N.Ai,
K.T.Duprez,
W.J.Welsh,
and
J.H.Toney
(2010).
Evolving carbapenemases: can medicinal chemists advance one step ahead of the coming storm?
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J Med Chem, 53,
3013-3027.
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S.M.Drawz,
and
R.A.Bonomo
(2010).
Three decades of beta-lactamase inhibitors.
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Clin Microbiol Rev, 23,
160-201.
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C.Bebrone,
H.Delbrück,
M.B.Kupper,
P.Schlömer,
C.Willmann,
J.M.Frère,
R.Fischer,
M.Galleni,
and
K.M.Hoffmann
(2009).
The structure of the dizinc subclass B2 metallo-beta-lactamase CphA reveals that the second inhibitory zinc ion binds in the histidine site.
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Antimicrob Agents Chemother, 53,
4464-4471.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
