7qor

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Structure of beta-lactamase TEM-171Structure of beta-lactamase TEM-171

Structural highlights

7qor is a 6 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.999Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BLAT_ECOLX TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors.

Publication Abstract from PubMed

The resistance of bacteria to beta-lactam antibiotics is primarily caused by the production of beta-lactamases. Here, novel crystal structures of the native beta-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 beta-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 beta-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 beta-lactamase inhibitors.

Crystal structures of the molecular class A beta-lactamase TEM-171 and its complexes with tazobactam.,Grigorenko VG, Petrova TE, Carolan C, Rubtsova MY, Uporov IV, Pereira J, Chojnowski G, Samygina VR, Lamzin VS, Egorov AM Acta Crystallogr D Struct Biol. 2022 Jul 1;78(Pt 7):825-834. doi: , 10.1107/S2059798322004879. Epub 2022 Jun 7. PMID:35775982[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Grigorenko VG, Petrova TE, Carolan C, Rubtsova MY, Uporov IV, Pereira J, Chojnowski G, Samygina VR, Lamzin VS, Egorov AM. Crystal structures of the molecular class A β-lactamase TEM-171 and its complexes with tazobactam. Acta Crystallogr D Struct Biol. 2022 Jul 1;78(Pt 7):825-834. PMID:35775982 doi:10.1107/S2059798322004879

7qor, resolution 2.00Å

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