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PDBsum entry 1i2s
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* Residue conservation analysis
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DOI no:
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Biochemistry
41:1877-1885
(2002)
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PubMed id:
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Crystal structures of the Bacillus licheniformis BS3 class A beta-lactamase and of the acyl-enzyme adduct formed with cefoxitin.
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E.Fonzé,
M.Vanhove,
G.Dive,
E.Sauvage,
J.M.Frère,
P.Charlier.
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ABSTRACT
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The Bacillus licheniformis BS3 beta-lactamase catalyzes the hydrolysis of the
beta-lactam ring of penicillins, cephalosporins, and related compounds. The
production of beta-lactamases is the most common and thoroughly studied cause of
antibiotic resistance. Although they escape the hydrolytic activity of the
prototypical Staphylococcus aureus beta-lactamase, many cephems are good
substrates for a large number of beta-lactamases. However, the introduction of a
7alpha-methoxy substituent, as in cefoxitin, extends their antibacterial
spectrum to many cephalosporin-resistant Gram-negative bacteria. The
7alpha-methoxy group selectively reduces the hydrolytic action of many
beta-lactamases without having a significant effect on the affinity for the
target enzymes, the membrane penicillin-binding proteins. We report here the
crystallographic structures of the BS3 enzyme and its acyl-enzyme adduct with
cefoxitin at 1.7 A resolution. The comparison of the two structures reveals a
covalent acyl-enzyme adduct with perturbed active site geometry, involving a
different conformation of the omega-loop that bears the essential catalytic
Glu166 residue. This deformation is induced by the cefoxitin side chain whose
position is constrained by the presence of the alpha-methoxy group. The
hydrolytic water molecule is also removed from the active site by the
7beta-carbonyl of the acyl intermediate. In light of the interactions and steric
hindrances in the active site of the structure of the BS3-cefoxitin acyl-enzyme
adduct, the crucial role of the conserved Asn132 residue is confirmed and a
better understanding of the kinetic results emerges.
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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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J.Vandenameele,
A.Matagne,
and
C.Damblon
(2010).
1H, 13C and 15N backbone resonance assignments for the BS3 class A β-lactamase from Bacillus licheniformis.
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Biomol NMR Assign,
4,
195-197.
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K.F.Kong,
L.Schneper,
and
K.Mathee
(2010).
Beta-lactam antibiotics: from antibiosis to resistance and bacteriology.
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APMIS,
118,
1.
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L.Vercheval,
C.Bauvois,
A.di Paolo,
F.Borel,
J.L.Ferrer,
E.Sauvage,
A.Matagne,
J.M.Frère,
P.Charlier,
M.Galleni,
and
F.Kerff
(2010).
Three factors that modulate the activity of class D β-lactamases and interfere with the post-translational carboxylation of Lys70.
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Biochem J,
432,
495-504.
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PDB codes:
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E.Sauvage,
A.Zervosen,
G.Dive,
R.Herman,
A.Amoroso,
B.Joris,
E.Fonzé,
R.F.Pratt,
A.Luxen,
P.Charlier,
and
F.Kerff
(2009).
Structural basis of the inhibition of class A beta-lactamases and penicillin-binding proteins by 6-beta-iodopenicillanate.
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J Am Chem Soc,
131,
15262-15269.
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PDB codes:
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E.Sauvage,
E.Fonzé,
B.Quinting,
M.Galleni,
J.M.Frère,
and
P.Charlier
(2006).
Crystal structure of the Mycobacterium fortuitum class A beta-lactamase: structural basis for broad substrate specificity.
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Antimicrob Agents Chemother,
50,
2516-2521.
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PDB code:
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F.Wang,
C.Cassidy,
and
J.C.Sacchettini
(2006).
Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics.
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Antimicrob Agents Chemother,
50,
2762-2771.
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PDB code:
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C.Fenollar-Ferrer,
J.Donoso,
J.Frau,
and
F.Muñoz
(2005).
Molecular modeling of Henry-Michaelis and acyl-enzyme complexes between imipenem and Enterobacter cloacae P99 beta-lactamase.
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Chem Biodivers,
2,
645-656.
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Y.Chen,
B.Shoichet,
and
R.Bonnet
(2005).
Structure, function, and inhibition along the reaction coordinate of CTX-M beta-lactamases.
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J Am Chem Soc,
127,
5423-5434.
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PDB codes:
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N.Rhazi,
P.Charlier,
D.Dehareng,
D.Engher,
M.Vermeire,
J.M.Frère,
M.Nguyen-Distèche,
and
E.Fonzé
(2003).
Catalytic mechanism of the Streptomyces K15 DD-transpeptidase/penicillin-binding protein probed by site-directed mutagenesis and structural analysis.
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Biochemistry,
42,
2895-2906.
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PDB codes:
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B.M.Beadle,
and
B.K.Shoichet
(2002).
Structural basis for imipenem inhibition of class C beta-lactamases.
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Antimicrob Agents Chemother,
46,
3978-3980.
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PDB code:
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R.A.Powers,
F.Morandi,
and
B.K.Shoichet
(2002).
Structure-based discovery of a novel, noncovalent inhibitor of AmpC beta-lactamase.
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Structure,
10,
1013-1023.
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PDB code:
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T.Shimamura,
A.Ibuka,
S.Fushinobu,
T.Wakagi,
M.Ishiguro,
Y.Ishii,
and
H.Matsuzawa
(2002).
Acyl-intermediate structures of the extended-spectrum class A beta-lactamase, Toho-1, in complex with cefotaxime, cephalothin, and benzylpenicillin.
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J Biol Chem,
277,
46601-46608.
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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
codes are
shown on the right.
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