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The Mechanisms of Catalysis by Metallo β-Lactamases
Joint Authors
Badarau, Adriana
Page, Michael I.
Source
Bioinorganic Chemistry and Applications
Issue
Vol. 2008, Issue 2008 (31 Dec. 2008), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2008-03-10
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Class B β-lactamases or metallo-β-lactamases (MBLs) require zinc ions to catalyse the hydrolysis of β-lactam antibiotics such as penicillins, cephalosporins, carbapenems, and cephamycins.
There are no clinically useful inhibitors against MBLs which are responsible for the resistance of some bacteria to antibiotics.
There are two metal-ion binding sites that have different zinc ligands but the exact roles of the metal-ion remain controversial, and distinguishing between their relative importance is complex.
The metal-ion can act as a Lewis acid by co-ordination to the β-lactam carbonyl oxygen to facilitate nucleophilic attack and stabilise the negative charge developed on this oxygen in the tetrahedral intermediate anion.
The metal-ion also lowers the pKa of the directly co-ordinated water molecule so that the metal-bound hydroxide ion is a better nucleophile than water and is used to attack the β-lactam carbonyl carbon.
An intrinsic property of binuclear metallo hydrolytic enzymes that depend on a metal-bound water both as the attacking nucleophile and as a ligand for the second metal-ion is that this water molecule, which is consumed during hydrolysis of the substrate, has to be replaced to maintain the catalytic cycle.
With MBL this is reflected in some unusual kinetic profiles.
American Psychological Association (APA)
Page, Michael I.& Badarau, Adriana. 2008. The Mechanisms of Catalysis by Metallo β-Lactamases. Bioinorganic Chemistry and Applications،Vol. 2008, no. 2008, pp.1-14.
https://search.emarefa.net/detail/BIM-987750
Modern Language Association (MLA)
Page, Michael I.& Badarau, Adriana. The Mechanisms of Catalysis by Metallo β-Lactamases. Bioinorganic Chemistry and Applications No. 2008 (2008), pp.1-14.
https://search.emarefa.net/detail/BIM-987750
American Medical Association (AMA)
Page, Michael I.& Badarau, Adriana. The Mechanisms of Catalysis by Metallo β-Lactamases. Bioinorganic Chemistry and Applications. 2008. Vol. 2008, no. 2008, pp.1-14.
https://search.emarefa.net/detail/BIM-987750
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-987750