5ls3

Publication Abstract from PubMed

Resistance to beta-lactam antibiotics mediated by metallo-beta-lactamases (MBLs) is a growing problem. We describe the use of protein-observe 19 F-NMR (PrOF NMR) to study the dynamics of the Sao Paulo MBL (SPM-1) from beta-lactam-resistant Pseudomonas aeruginosa. Cysteinyl variants on the alpha3 and L3 regions, which flank the di-ZnII active site, were selectively 19 F-labeled using 3-bromo-1,1,1-trifluoroacetone. The PrOF NMR results reveal roles for the mobile alpha3 and L3 regions in the binding of both inhibitors and hydrolyzed beta-lactam products to SPM-1. These results have implications for the mechanisms and inhibition of MBLs by beta-lactams and non-beta-lactams and illustrate the utility of PrOF NMR for efficiently analyzing metal chelation, identifying new binding modes, and studying protein binding from a mixture of equilibrating isomers.

19 F-NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the Sao Paulo Metallo-beta-Lactamase.,Abboud MI, Hinchliffe P, Brem J, Macsics R, Pfeffer I, Makena A, Umland KD, Rydzik AM, Li GB, Spencer J, Claridge TD, Schofield CJ Angew Chem Int Ed Engl. 2017 Mar 2. doi: 10.1002/anie.201612185. PMID:28252254^[1]

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