Metallo-beta-lactamase-Catalyzed Hydrolysis of Cephalosporins: Some Mechanistic Insights into the Effect of Heterocyclic Thiones on Enzyme Activity

Tamilselvi, A and Mugesh, Govindasamy (2011) Metallo-beta-lactamase-Catalyzed Hydrolysis of Cephalosporins: Some Mechanistic Insights into the Effect of Heterocyclic Thiones on Enzyme Activity. In: Inorganic Chemistry, 50 (3). pp. 749-756.

	PDF Metallo.pdf - Published Version Restricted to Registered users only Download (2MB) | Request a copy
	PDF ic100253k_si_001.pdf - Published Supplemental Material Restricted to Registered users only Download (275kB) | Request a copy
	Other ic100253k_si_002.cif - Published Supplemental Material Restricted to Registered users only Download (28kB) | Request a copy
	Other ic100253k_si_003.cif - Published Supplemental Material Restricted to Registered users only Download (17kB) | Request a copy

Abstract

The hydrolysis of beta-lactam antibiotics using zinc-containing metallo-beta-lactamases (m beta l) is one of the major bacterial defense systems. These enzymes can catalyze the hydrolysis of a variety of antibiotics including the latest generation of cephalosporins, cephamycins, and imipenem. It is shown in this paper that the cephalosporins having heterocyclic - SR side chains are less prone to m beta l-mediated hydrolysis than the antibiotics that do not have such side chains. This is partly due to the inhibition of enzyme activity by the thione moieties eliminated during hydrolysis. When the enzymatic hydrolysis of oxacillin was carried out in the presence of heterocyclic thiones such as MU, MDT, DMETT, and MMA, the catalytic activity of the enzyme was inhibited significantly by these compounds. Although the heterocyclic - SR moieties eliminated from the beta-lactams upon hydrolysis undergo a rapid tautomerism between thione and thiol forms, these compounds act as thiolate ligands toward zinc(II) ions. The structural characterization of two model tetranuclear zinc(II) thiolate complexes indicates that the -SR side chains eliminated from the antibiotics may interact with the zinc(II) metal center of m beta l through their sulfur atoms.

Item Type:	Journal Article
Publication:	Inorganic Chemistry
Publisher:	American chemical society
Additional Information:	Copyright of this article belongs to American chemical society.
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	08 Apr 2011 05:59
Last Modified:	08 Apr 2011 05:59
URI:	http://eprints.iisc.ac.in/id/eprint/36585

Actions (login required)

View Item