title: Inhibition of the SHV-1 beta-lactamase by sulfones: crystallographic observation of two reaction intermediates with tazobactam.
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.
authors.affiliation: Department of Molecular and Cell Biology, The University of Connecticut, Storrs, CT 06269-3125, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Kuzin
authors.forename: M
authors.initials: M
authors.lastname: Nukaga
authors.forename: Y
authors.initials: Y
authors.lastname: Nukaga
authors.forename: A
authors.initials: A
authors.lastname: Hujer
authors.forename: R A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: J R
authors.initials: JR
authors.lastname: Knox
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007711:Klebsiella pneumoniae / Q000201:enzymology; D008958:Models, Molecular; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D012997:Solvents; D013450:Sulfones / Q000737:chemistry*; D000078142:Tazobactam; D013696:Temperature; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D012997:Solvents; D013450:Sulfones; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; C054882:beta-lactamase PIT-2; D001618:beta-Lactamases; D000078142:Tazobactam