Crystal structures of the molecular class A β-lactamase TEM-171 and its complexes with tazobactam

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.

Авторы: Grigorenko Vitaly G., Petrova Tatiana E., Carolan Ciaran, Rubtsova Maya Yu, Uporov Igor V., Pereira Joana, Chojnowski Grzegorz, Samygina Valeriya R., Lamzin Victor S., Egorov Alexey M.
Журнал: ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
Том: 78
Номер: 7
Год издания: 2022
Первая страница: 825
Последняя страница: 834
DOI: 10.1107/S2059798322004879
Аннотация: 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.
Добавил в систему: Григоренко Виталий Георгиевич

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Crystal structures of the molecular class A β-lactamase TEM-171 and its complexes with tazobactamстатья

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