PDBsum entry 2m5c

Hydrolase

PDB id: 2m5c

Contents

Protein chain

227 a.a.

Metals

_ZN ×2

PDB id:

2m5c

Name:

Hydrolase

Title:

Solution structure of the bacillus cereus metallo-beta-lactamase bcii

Structure:

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

Source:

Bacillus cereus. Organism_taxid: 1396. Strain: 569/h. Gene: blm. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

A.I.Karsisiotis,C.F.Damblon,G.C.K.Roberts

Key ref:

A.I.Karsisiotis et al. (2013). Solution structures of the Bacillus cereus metallo-β-lactamase BcII and its complex with the broad spectrum inhibitor R-thiomandelic acid. Biochem J, 456, 397-407. PubMed id: 24059435 DOI: 10.1042/BJ20131003

Date:

20-Feb-13 Release date: 09-Oct-13

Protein chain

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

Seq: 257 a.a.

Struc: 227 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: 10.1042/BJ20131003

Biochem J 456:397-407 (2013)

PubMed id: 24059435

Solution structures of the Bacillus cereus metallo-β-lactamase BcII and its complex with the broad spectrum inhibitor R-thiomandelic acid.

A.I.Karsisiotis, C.F.Damblon, G.C.Roberts.

ABSTRACT

Metallo-β-lactamases, enzymes which inactivate β-lactam antibiotics, are of increasing biological and clinical significance as a source of antibiotic resistance in pathogenic bacteria. In the present study we describe the high-resolution solution NMR structures of the Bacillus cereus metallo-β-lactamase BcII and of its complex with R-thiomandelic acid, a broad-spectrum inhibitor of metallo-β-lactamases. This is the first reported solution structure of any metallo-β-lactamase. There are differences between the solution structure of the free enzyme and previously reported crystal structures in the loops flanking the active site, which are important for substrate and inhibitor binding and catalysis. The binding of R-thiomandelic acid and the roles of active-site residues are defined in detail. Changes in the enzyme structure upon inhibitor binding clarify the role of the mobile β3-β4 loop. Comparisons with other metallo-β-lactamases highlight the roles of individual amino-acid residues in the active site and the β3-β4 loop in inhibitor binding and provide information on the basis of structure-activity relationships among metallo-β-lactamase inhibitors.