6OOJ

CTX-M-14 Beta Lactamase with Compound 14

Summary for 6OOJ

• Entry DOI: 10.2210/pdb6ooj/pdb
• Descriptor: Beta-lactamase, 3-(1H-pyrazol-1-yl)-N-[3-(1H-tetrazol-5-yl)phenyl]-5-(trifluoromethyl)benzamide (3 entities in total)
• Functional Keywords: beta-lactamase, esbl, non covalent complex, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 57564.35

Authors

Kemp, M.,Chen, Y. (deposition date: 2019-04-23, release date: 2020-07-01, Last modification date: 2024-11-06)

Primary citation

DeFrees, K.,Kemp, M.T.,ElHilali-Pollard, X.,Zhang, X.,Mohamed, A.,Chen, Y.,Renslo, A.R.
An Empirical Study of Amide-Heteroarene pi-Stacking Interactions Using Reversible Inhibitors of a Bacterial Serine Hydrolase.
Org Chem Front, 6:1749-1756, 2019

PubMed Abstract: Compared to aryl-aryl π-stacking interactions, the analogous stacking of heteroarenes on amide π systems is less well understood and vastly underutilized in structure-based drug design. Recent theoretical studies have delineated the important geometric coordinates of the interaction, some of which have been confirmed with synthetic model systems based on Rebek imides. Unfortunately, a broadly useful and tractable protein-ligand model system of this interaction has remained elusive. Here we employed a known inhibitor scaffold to study π-stacking of diverse heteroarene substituents on the amide face of Gly238 in the cephalosporinases CTX-M-14 and CTX-M-27. Biochemical inhibition constants ( ) and biophysical binding constants ( ) were determined for nineteen new analogues against both enzymes, while multiple high-resolution co-crystal structures revealed remarkably consistent placement of the probe heteroarene on Gly238. The data presented support the predicted importance of opposing dipoles in amide-heteroarene interactions and should be useful for evaluating other theoretical predictions concerning these interactions.

PubMed: 32774871
DOI: 10.1039/c9qo00342h

Experimental method

X-RAY DIFFRACTION (1.4 Å)