Inhibition of the SHV-1 beta-lactamase by sulfones: crystallographic observation of two reaction intermediates with tazobactam

Biochemistry. 2001 Feb 13;40(6):1861-6. doi: 10.1021/bi0022745.

Abstract

Two species resulting from the reaction of the SHV-1 class A beta-lactamase with the sulfone inhibitor tazobactam have been trapped at 100 K and mapped by X-ray crystallography at 2.0 A resolution. An acyclic form of tazobactam is covalently bonded to the catalytic Ser70 side chain, and a second species, a five-atom vinyl carboxylic acid fragment of tazobactam, is bonded to Ser130. It is proposed that the electron density map of the crystal is a composite picture of two complexes, each with only a single bound species. It is estimated that the two complexes exist in the crystal in approximately equal populations. Results are discussed in relation to the mechanism-based inhibition of class A beta-lactamases by the similar inhibitors sulbactam and clavulanic acid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry*
  • Hydrogen-Ion Concentration
  • Klebsiella pneumoniae / enzymology
  • Models, Molecular
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / chemistry*
  • Solvents
  • Sulfones / chemistry*
  • Tazobactam
  • Temperature
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / chemistry*

Substances

  • Enzyme Inhibitors
  • Solvents
  • Sulfones
  • beta-Lactamase Inhibitors
  • Penicillanic Acid
  • beta-lactamase PIT-2
  • beta-Lactamases
  • Tazobactam

Associated data

  • PDB/1G56