Inhibition of the SHV-1 -Lactamase by Sulfones: Crystallographic Observation of Two Reaction Intermediates with Tazob
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- 作者：Alexandre P. Kuzin ; Michiyoshi Nukaga ; Yasuko Nukaga ; Andrea Hujer ; Robert A. Bonomo ; and James R. Knox
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：February 13, 2001
- 年：2001
- 卷：40
- 期：6
- 页码：1861 - 1866
- 全文大小：147K
- 年卷期：v.40,no.6(February 13, 2001)
- ISSN：1520-4995
文摘
Two species resulting from the reaction of the SHV-1 class A 
-lactamase with the sulfoneinhibitor 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 theelectron density map of the crystal is a composite picture of two complexes, each with only a singlebound 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 -lactamases by the similarinhibitors sulbactam and clavulanic acid.
-lactamase with the sulfoneinhibitor 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 theelectron density map of the crystal is a composite picture of two complexes, each with only a singlebound 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 -lactamases by the similarinhibitors sulbactam and clavulanic acid.