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PDBsum entry 1i2s
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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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Crystal structures of the bacillus licheniformis bs3 class a beta-Lactamase and of the acyl-Enzyme adduct formed with cefoxitin.
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Authors
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E.Fonzé,
M.Vanhove,
G.Dive,
E.Sauvage,
J.M.Frère,
P.Charlier.
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Ref.
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Biochemistry, 2002,
41,
1877-1885.
[DOI no: ]
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PubMed id
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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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Secondary reference #1
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Title
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Unexpected influence of a c-Terminal-Fused his-Tag on the processing of an enzyme and on the kinetic and folding parameters.
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Authors
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P.Ledent,
C.Duez,
M.Vanhove,
A.Lejeune,
E.Fonzé,
P.Charlier,
F.Rhazi-Filali,
I.Thamm,
G.Guillaume,
B.Samyn,
B.Devreese,
J.Van beeumen,
J.Lamotte-Brasseur,
J.M.Frère.
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Ref.
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Febs Lett, 1997,
413,
194-196.
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PubMed id
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