PDBsum entry 5ls3

Hydrolase

PDB id: 5ls3

Contents

Protein chains

245 a.a.

Metals

_ZN ×5

Waters ×374

PDB id:

5ls3

Name:

Hydrolase

Title:

Crystal structure of metallo-beta-lactamase spm-1 with y58c mutation

Structure:

Beta-lactamase imp-1. Chain: b, a. Synonym: beta-lactamase spm-1,metallo-b-lactamase,metallo-beta- lactamase blaspm-1,spm-1. Engineered: yes. Mutation: yes

Source:

Pseudomonas aeruginosa. Organism_taxid: 287. Gene: spm-1, bla spm-1, blaspm-1, ccbh4851_00081, icepaesp_00028. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: plyss.

Resolution:

1.75Å R-factor: 0.167 R-free: 0.184

Authors:

P.Hinchliffe,J.Spencer

Key ref:

M.I.Abboud et al. (2017). (19) F-NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo-β-Lactamase. Angew Chem Int Ed Engl, 56, 3862-3866. PubMed id: 28252254 DOI: 10.1002/anie.201612185

Date:

22-Aug-16 Release date: 15-Mar-17

Protein chains

Q8G9Q0  (Q8G9Q0_PSEAI) -  beta-lactamase from Pseudomonas aeruginosa

Seq: 276 a.a.

Struc: 245 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.5.2.6 - beta-lactamase.
• Pathway: Penicillin Biosynthesis and Metabolism
• Reaction: a beta-lactam + H2O = a substituted beta-amino acid
• Cofactor: Zn(2+)

DOI no: 10.1002/anie.201612185

Angew Chem Int Ed Engl 56:3862-3866 (2017)

PubMed id: 28252254

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

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.

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.