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PDBsum entry 1kvm
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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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Structural milestones in the reaction pathway of an amide hydrolase: substrate, Acyl, And product complexes of cephalothin with ampc beta-Lactamase.
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Authors
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B.M.Beadle,
I.Trehan,
P.J.Focia,
B.K.Shoichet.
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Ref.
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Structure, 2002,
10,
413-424.
[DOI no: ]
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PubMed id
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Abstract
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Beta-lactamases hydrolyze beta-lactam antibiotics and are the leading cause of
bacterial resistance to these drugs. Although beta-lactamases have been
extensively studied, structures of the substrate-enzyme and product-enzyme
complexes have proven elusive. Here, the structure of a mutant AmpC in complex
with the beta-lactam cephalothin in its substrate and product forms was
determined by X-ray crystallography to 1.53 A resolution. The acyl-enzyme
intermediate between AmpC and cephalothin was determined to 2.06 A resolution.
The ligand undergoes a dramatic conformational change as the reaction
progresses, with the characteristic six-membered dihydrothiazine ring of
cephalothin rotating by 109 degrees. These structures correspond to all three
intermediates along the reaction path and provide insight into substrate
recognition, catalysis, and product expulsion.
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Figure 3.
Figure 3. Stereoviews of Key Interactions Observed within
Each Complexed Structure(A) S64G/cephalothin enzyme-substrate
complex.(B) WT/cephalothin acyl complex.(C) S64G/cephalothin
enzyme-product complex.Atoms are colored as in Figure 2, except
that the carbon atoms of the substrate are green, the acyl
ligand is orange, and the product is magenta, for clarity.
Dashed yellow lines indicate interactions within hydrogen
bonding distance; interaction distances are given in Table 2.
Hydrogen bonds between protein residues are not shown. Figures 3
and 4 were generated using MidasPlus [53].
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2002,
10,
413-424)
copyright 2002.
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