(19) F-NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo-?-Lactamase.
 

(19) F-NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo-?-Lactamase.

http://www.bionmr.com//www.ncbi.nlm....x30_orange.png Related Articles (19) F-NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo-?-Lactamase.

Angew Chem Int Ed Engl. 2017 Mar 02;:

Authors: Abboud MI, Hinchliffe P, Brem J, Macsics R, Pfeffer I, Makena A, Umland KD, Rydzik AM, Li GB, Spencer J, Claridge TD, Schofield CJ

Abstract
Resistance to ?-lactam antibiotics mediated by metallo-?-lactamases (MBLs) is a growing problem. We describe the use of protein-observe (19) F-NMR (PrOF NMR) to study the dynamics of the São Paulo MBL (SPM-1) from ?-lactam-resistant Pseudomonas aeruginosa. Cysteinyl variants on the ?3 and L3 regions, which flank the di-Zn(II) active site, were selectively (19) F-labeled using 3-bromo-1,1,1-trifluoroacetone. The PrOF NMR results reveal roles for the mobile ?3 and L3 regions in the binding of both inhibitors and hydrolyzed ?-lactam products to SPM-1. These results have implications for the mechanisms and inhibition of MBLs by ?-lactams and non-?-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.


PMID: 28252254 [PubMed - as supplied by publisher]



More...