PDBsum entry 4wz4

Hydrolase/hydrolase inhibitor

PDB id: 4wz4

Contents

Protein chain

360 a.a.

Ligands

GOL

3VU

Waters ×432

PDB id:

4wz4

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of p. Aeruginosa ampc

Structure:

Beta-lactamase. Chain: a. Synonym: cephalosporinase. Engineered: yes

Source:

Pseudomonas aeruginosa pao1. Organism_taxid: 208964. Strain: atcc 15692 / pao1 / 1c / prs 101 / lmg 12228. Gene: ampc, pa4110. Expressed in: pseudomonas aeruginosa pao1. Expression_system_taxid: 208964

Resolution:

1.05Å R-factor: 0.187 R-free: 0.199

Authors:

A.D.Ferguson

Key ref:

D.C.McKinney et al. (2015). 4,5-Disubstituted 6-Aryloxy-1,3-dihydrobenzo[c][1,2]oxaboroles Are Broad-Spectrum Serine β-Lactamase Inhibitors. Acs Infect Dis, 1, 310-316. PubMed id: 27622821 DOI: 10.1021/acsinfecdis.5b00031

Date:

18-Nov-14 Release date: 05-Aug-15

Protein chain

P24735  (AMPC_PSEAE) -  Beta-lactamase from Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

Seq: 397 a.a.

Struc: 360 a.a.

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: 10.1021/acsinfecdis.5b00031

Acs Infect Dis 1:310-316 (2015)

PubMed id: 27622821

4,5-Disubstituted 6-Aryloxy-1,3-dihydrobenzo[c][1,2]oxaboroles Are Broad-Spectrum Serine β-Lactamase Inhibitors.

D.C.McKinney, F.Zhou, C.J.Eyermann, A.D.Ferguson, D.B.Prince, J.Breen, R.A.Giacobbe, S.Lahiri, J.C.Verheijen.

ABSTRACT

Bacterially expressed β-lactamases are rapidly eroding the clinical utility of the important β-lactam class of antibacterials, significantly impairing our ability to fight serious bacterial infections. This paper describes a study of oxaborole-derived β-lactamase inhibitors in which crystal structures and computational modeling aided in the rational design of analogues with improved spectrum of activity against class A, C, and D enzymes. Crystal structures of two of these inhibitors covalently bound to two different serine β-lactamases, class C Pseudomonas aeruginosa AmpC and class D OXA-10, are described herein. Improved physicochemical properties as well as increased activity against an array of β-lactamases resulted in substantial restoration of susceptibility to ceftazidime in Escherichia coli and Klebsiella pneumoniae.