Inhibition of the SHV-1 β-Lactamase by Sulfones: Crystallographic Observation of Two Reaction Intermediates with Tazobactam,

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Abstract
Two species resulting from the reaction of the SHV-1 class A β-lactamase with the sulfone inhibitor tazobactam have been trapped at 100 K and mapped by X-ray crystallography at 2.0 Å 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 β-lactamases by the similar inhibitors sulbactam and clavulanic acid.