Linked Life Data

18702503

Source:http://linkedlifedata.com/resource/pubmed/id/18702503

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
2008-9-4
pubmed:abstractText
All three classes of serine beta-lactamases are inhibited at micromolar levels by 1:1 complexes of catechols with vanadate. Vanadate reacts with catechols at submillimolar concentrations in aqueous buffer at neutral pH in several steps, initially forming 1:1, 1:2, and, possibly, 1:3 complexes. Formation of these complexes is followed by the slower reduction of vanadate (V (V)) to vanadyl (V (IV)) and oxidation of the catechol. Vanadyl-catechol complexes, however, do not inhibit the beta-lactamases. Rate and equilibrium constants of formation of the 1:1 and 1:2 complexes of vanadate with catechol itself and with 2,3-dihydroxynaphthalene were measured by stopped-flow spectrophotometry. Typical examples of all three classes of serine beta-lactamases (the class A TEM-2, class C P99, and class D OXA-1 enzymes) were competitively inhibited by the 1:1 vanadate-catechol complexes. The inhibition was modestly enhanced by hydrophobic substituents on the catechol. The 1:1 vanadate complexes are considerably better inhibitors of the P99 beta-lactamase than 1:1 complexes of catechol with boric acid and are likely to contain penta- or hexacoordinated vanadium rather than tetracooordinated. Molecular modeling showed that a pentacoordinated 1:1 vanadate-catechol complex readily fits into the class C beta-lactamase active site with coordination to the nucleophilic serine hydroxyl oxygen. Such complexes may resemble the pentacoordinated transition states of phosphyl transfer, a reaction also catalyzed by beta-lactamases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9467-74
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Inhibition of serine beta-lactamases by vanadate-catechol complexes.
pubmed:affiliation
Department of Chemistry, Wesleyan University, Middletown, Connecticut 06459, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural