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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1sml

E.C. namebeta-lactamase
SpeciesXanthomonas maltophilia ()
E.C. Number (IntEnz) 3.5.2.6
CSA Homologues of 1sml
CSA Entries With UniProtID P52700
CSA Entries With EC Number 3.5.2.6
PDBe Entry 1sml
PDBSum Entry 1sml
MACiE Entry M0258

Literature Report

IntroductionThe L1 metallo-beta-lactamase from Stenotrophomonas maltophilia is unique among beta-lactamases in that it is tetrameric. S. maltophilia has emerged as a significant hospital-derived pathogen of immunocompromised hosts such as cancer, cystic fibrosis and transplant patients. L1 is localised to the periplasm and hydrolyses carbapenem drugs, conferring antibiotic resistance.
L1 is of the class 3a metallo-beta-lactamases and binds two Zn(II) ions for the hydrolytic reaction.
Mechansim1) Zn1 polarises the substrate carbonyl to activate the group as an electrophile.
2) A hydroxide ion bridges the zinc ions. This is nucleophilic and attacks the substrate carbonyl.
3) A tetrahedral transition state is stabilised by Zn1, a helix dipole and Tyr 191.
4) The substrate ring amide is cleaved, with the nitrogen leaving as an anion, stabilised by Zn2 acting as a superacid. The other end of the amide is a carboxylic acid.
5) A water molecule, acidified by the zinc ions, protonates the nitroanion. The resulting hydroxide can be nucleophilic in the next catalytic cycle.
Reaction

Catalytic Sites for 1sml

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA191212macie:sideChainTyr 191 is part of the oxyanion hole, stabilising the tetrahedral transition state. This may be directly or via a water molecule.

Literature References

Notes:
Wang Z
On the mechanism of the metallo-beta-lactamase from Bacteroides fragilis.
Biochemistry 1999 38 10013-10023
PubMed: 10433708
Ullah JH
The crystal structure of the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia at 1.7 A resolution.
J Mol Biol 1998 284 125-136
PubMed: 9811546
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