5LS3

Crystal structure of metallo-beta-lactamase SPM-1 with Y58C mutation

Summary for 5LS3

• Entry DOI: 10.2210/pdb5ls3/pdb
• Descriptor: Beta-lactamase IMP-1, ZINC ION (3 entities in total)
• Functional Keywords: metallo-beta-lactamase, carbapenemase, hydrolase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 56061.34

Authors

Hinchliffe, P.,Spencer, J. (deposition date: 2016-08-22, release date: 2017-03-15, Last modification date: 2024-01-17)

Primary citation

Abboud, M.I.,Hinchliffe, P.,Brem, J.,Macsics, R.,Pfeffer, I.,Makena, A.,Umland, K.D.,Rydzik, A.M.,Li, G.B.,Spencer, J.,Claridge, T.D.,Schofield, C.J.
(19) F-NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the Sao Paulo Metallo-beta-Lactamase.
Angew. Chem. Int. Ed. Engl., 56:3862-3866, 2017

PubMed Abstract: Resistance to β-lactam antibiotics mediated by metallo-β-lactamases (MBLs) is a growing problem. We describe the use of protein-observe F-NMR (PrOF NMR) to study the dynamics of the São Paulo MBL (SPM-1) from β-lactam-resistant Pseudomonas aeruginosa. Cysteinyl variants on the α3 and L3 regions, which flank the di-Zn active site, were selectively F-labeled using 3-bromo-1,1,1-trifluoroacetone. The PrOF NMR results reveal roles for the mobile α3 and L3 regions in the binding of both inhibitors and hydrolyzed β-lactam products to SPM-1. These results have implications for the mechanisms and inhibition of MBLs by β-lactams and non-β-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.

PubMed: 28252254
DOI: 10.1002/anie.201612185

Experimental method

X-RAY DIFFRACTION (1.754 Å)