7QLP

Structure of beta-lactamase TEM-171 complexed with tazobactam intermediate at 2.3 A resolution

7QLP の概要

• エントリーDOI: 10.2210/pdb7qlp/pdb
• 分子名称: Beta-lactamase TEM, TAZOBACTAM INTERMEDIATE, ACETATE ION, ... (6 entities in total)
• 機能のキーワード: beta-lactamase, beta-lactamase inhibitor, hydrolase-inhibitor complex, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 175188.61

構造登録者

Hakanpaa, J.,Petrova, T.,Samygina, V.R.,Lamzin, V.S.,Egorov, A.M. (登録日: 2021-12-20, 公開日: 2022-07-13, 最終更新日: 2024-11-13)

主引用文献

Grigorenko, V.G.,Petrova, T.E.,Carolan, C.,Rubtsova, M.Y.,Uporov, I.V.,Pereira, J.,Chojnowski, G.,Samygina, V.R.,Lamzin, V.S.,Egorov, A.M.
Crystal structures of the molecular class A beta-lactamase TEM-171 and its complexes with tazobactam.
Acta Crystallogr D Struct Biol, 78:825-834, 2022

PubMed Abstract: The resistance of bacteria to β-lactam antibiotics is primarily caused by the production of β-lactamases. Here, novel crystal structures of the native β-lactamase TEM-171 and two complexes with the widely used inhibitor tazobactam are presented, alongside complementary data from UV spectroscopy and fluorescence quenching. The six chemically identical β-lactamase molecules in the crystallographic asymmetric unit displayed different degrees of disorder. The tazobactam intermediate was covalently bound to the catalytic Ser70 in the trans-enamine configuration. While the conformation of tazobactam in the first complex resembled that in published β-lactamase-tazobactam structures, in the second complex, which was obtained after longer soaking of the native crystals in the inhibitor solution, a new and previously unreported tazobactam conformation was observed. It is proposed that the two complexes correspond to different stages along the deacylation path of the acyl-enzyme intermediate. The results provide a novel structural basis for the rational design of new β-lactamase inhibitors.

PubMed: 35775982
DOI: 10.1107/S2059798322004879

実験手法

X-RAY DIFFRACTION (2.3 Å)