PDBsum entry 5ls3

Hydrolase

PDB id: 5ls3

Contents

Protein chains

245 a.a.

Metals

_ZN ×5

Waters ×374

References listed in PDB file

Key reference

• Title: (19) f-Nmr reveals the role of mobile loops in product and inhibitor binding by the são paulo metallo-β-Lactamase.
• Authors: M.I.Abboud, P.Hinchliffe, J.Brem, R.Macsics, I.Pfeffer, A.Makena, K.D.Umland, A.M.Rydzik, G.B.Li, J.Spencer, T.D.Claridge, C.J.Schofield.
• Ref.: Angew Chem Int Ed Engl, 2017, 56, 3862-3866. [DOI no: 10.1002/anie.201612185]
• PubMed id: 28252254

Abstract

Resistance to β-lactam antibiotics mediated by metallo-β-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 β-lactam-resistant Pseudomonas aeruginosa. Cysteinyl variants on the α3 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 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.