PDBsum entry 4c1c

Hydrolase

PDB id: 4c1c

Contents

Protein chain

220 a.a.

Ligands

GOL ×2

SO4

MCO

Metals

_ZN ×2

Waters ×268

PDB id:

4c1c

Name:

Hydrolase

Title:

Crystal structure of the metallo-beta-lactamase bcii with d-captopril

Structure:

Beta-lactamase 2. Chain: a. Fragment: residues 31-257. Synonym: beta-lactamase ii, cephalosporinase, penicillinase, bcii. Engineered: yes

Source:

Bacillus cereus. Organism_taxid: 1396. Strain: 569/h/9. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss. Other_details: chromosome derived.

Resolution:

1.18Å R-factor: 0.120 R-free: 0.136

Authors:

D.Zollman,J.Brem,M.A.Mcdonough,S.S.Van Berkel,C.J.Schofield

Key ref:

J.Brem et al. (2015). Structural Basis of Metallo-β-Lactamase Inhibition by Captopril Stereoisomers. Antimicrob Agents Chemother, 60, 142-150. PubMed id: 26482303 DOI: 10.1128/AAC.01335-15

Date:

12-Aug-13 Release date: 27-Aug-14

Protein chain

P04190  (BLA2_BACCE) -  Metallo-beta-lactamase type 2 from Bacillus cereus

Seq: 257 a.a.

Struc: 220 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: 10.1128/AAC.01335-15

Antimicrob Agents Chemother 60:142-150 (2015)

PubMed id: 26482303

Structural Basis of Metallo-β-Lactamase Inhibition by Captopril Stereoisomers.

J.Brem, S.S.van Berkel, D.Zollman, S.Y.Lee, O.Gileadi, P.J.McHugh, T.R.Walsh, M.A.McDonough, C.J.Schofield.

ABSTRACT

β-Lactams are the most successful antibacterials, but their effectiveness is threatened by resistance, most importantly by production of serine- and metallo-β-lactamases (MBLs). MBLs are of increasing concern because they catalyze the hydrolysis of almost all β-lactam antibiotics, including recent-generation carbapenems. Clinically useful serine-β-lactamase inhibitors have been developed, but such inhibitors are not available for MBLs. l-Captopril, which is used to treat hypertension via angiotensin-converting enzyme inhibition, has been reported to inhibit MBLs by chelating the active site zinc ions via its thiol(ate). We report systematic studies on B1 MBL inhibition by all four captopril stereoisomers. High-resolution crystal structures of three MBLs (IMP-1, BcII, and VIM-2) in complex with either the l- or d-captopril stereoisomer reveal correlations between the binding mode and inhibition potency. The results will be useful in the design of MBL inhibitors with the breadth of selectivity required for clinical application against carbapenem-resistant Enterobacteriaceae and other organisms causing MBL-mediated resistant infections.