7QNK

Structure of beta-lactamase TEM-171 complexed with tazobactam intermediate at 2.5 A resolution

Summary for 7QNK

• Entry DOI: 10.2210/pdb7qnk/pdb
• Related: 7QLP
• Descriptor: Beta-lactamase TEM, TAZOBACTAM INTERMEDIATE, ACETATE ION, ... (4 entities in total)
• Functional Keywords: beta-lactamase, beta-lactamase inhibitor, hydrolase-inhibitor complex, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 6
• Total formula weight: 175365.75

Authors

Hakanpaa, J.,Petrova, T.,Samygina, V.R.,Lamzin, V.S.,Egorov, A.M. (deposition date: 2021-12-21, release date: 2022-07-13, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)