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Search The CSA
PDB ID
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Catalytic Site Atlas

CSA LITERATURE entry for 1m6k

E.C. namebeta-lactamase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 3.5.2.6
CSA Homologues of 1m6kThere are 66 Homologs
CSA Entries With UniProtID P13661
CSA Entries With EC Number 3.5.2.6
PDBe Entry 1m6k
PDBSum Entry 1m6k
MACiE Entry M0210

Literature Report

IntroductionClass D beta lactamases are able to break down oxacillin and cloxacillin thus playing a vital role in antibiotic resistance in bacteria as they can prevent these compounds from inhibiting the DD peptidases involved in bacterial cell wall synthesis. As part of the family of serine beta lactamases, which also includes classes A B and C of the beta lactamases, they share significant homology with the DD peptidases, indicating that they diverged from a common ancestor. However, they are able to hydrolyse the acyl enzyme intermediate that forms through initial nucleophilic attack on the beta-lactam ring much more quickly, thus do not become inhibited by the beta lactams in the same way.
MechansimSer 67, having been deprotonated by carboxylated Lys 70, is able to act as a nucleophile to attack the strained peptide bond in the beta lactam ring and form a tetrahedral intermediate, stabilised by the backbone amide of Ser 67. The collapse of this intermediate, facilliatated by protonation of the leaving group by the epsilon NH of the carboxylated Lys 70, results in an acyl enzyme intermediate. This can be hydrolysed because a water molecule, activated by deprotonation by Lys 70, can attack the intermediate, resulting in the formation of a carboxylic acid and the regeneration of the catalytically active Ser 67 residue.
Reaction

Catalytic Sites for 1m6k

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA6771macie:sideChainActs as nucleophile to attack the beta lactam ring, forming an oxyanion intermediate which is stabilised by a hydrogen bond between its main chain amide and the oxyanion. Subsequent collapse and hydrolysis of the intermediates results in product formation.
SerA6771macie:mainChainAmideActs as nucleophile to attack the beta lactam ring, forming an oxyanion intermediate which is stabilised by a hydrogen bond between its main chain amide and the oxyanion. Subsequent collapse and hydrolysis of the intermediates results in product formation.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerB6771macie:sideChainError

Literature References

Notes:
Sun T
Comparison of beta-lactamases of classes A and D: 1.5-A crystallographic structure of the class D OXA-1 oxacillinase.
Protein Sci 2003 12 82-91
PubMed: 12493831
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