Linked Life Data

16081098

Source:http://linkedlifedata.com/resource/pubmed/id/16081098

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-8-29
pubmed:databankReference
pubmed:abstractText
Human carboxylesterase 1 (hCE1) exhibits broad substrate specificity and is involved in xenobiotic processing and endobiotic metabolism. We present and analyze crystal structures of hCE1 in complexes with the cholesterol-lowering drug mevastatin, the breast cancer drug tamoxifen, the fatty acyl ethyl ester (FAEE) analogue ethyl acetate, and the novel hCE1 inhibitor benzil. We find that mevastatin does not appear to be a substrate for hCE1, and instead acts as a partially non-competitive inhibitor of the enzyme. Similarly, we show that tamoxifen is a low micromolar, partially non-competitive inhibitor of hCE1. Further, we describe the structural basis for the inhibition of hCE1 by the nanomolar-affinity dione benzil, which acts by forming both covalent and non-covalent complexes with the enzyme. Our results provide detailed insights into the catalytic and non-catalytic processing of small molecules by hCE1, and suggest that the efficacy of clinical drugs may be modulated by targeted hCE1 inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
352
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
165-77
pubmed:dateRevised
2010-5-20
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil.
pubmed:affiliation
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural