Linked Life Data

17847090

Source:http://linkedlifedata.com/resource/pubmed/id/17847090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-2-27
pubmed:abstractText
Human fatty acid synthase (hFAS) thioesterase domain (TE) is an attractive drug target to treat obesity and cancer. On the basis of the recently published crystal structure of TE domain of hFAS, we performed molecular surface analysis and docking study to characterize the molecular interactions between the enzyme and its various ligands. Surface analysis identified the ligand-binding pocket of TE domain that encompasses the catalytic triad of Ser2308, His2481, Asp2338. Docking of palmitate, the main biological product of hFAS, into this pocket revealed the ligand-binding mode, in which the hydrophobic interactions are the dominant driving forces. The catalytic mechanism of TE domain can also be well explained based on the generated TE-palmitate complex structure. Moreover, the comparison of the binding modes of five fatty acids with chain lengths ranging from 12 to 20 carbons confirmed that the ligand binding pocket of TE domain is a decisive factor in chain length specificity. In addition, docking of two known TE inhibitors, c75 and orlistat revealed the pharmacophore of these hFAS TE inhibitors, which will prove useful in structure-based drug design against this important target.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1097-0134
pubmed:author
pubmed:copyrightInfo
2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1228-34
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Molecular docking study of the interactions between the thioesterase domain of human fatty acid synthase and its ligands.
pubmed:affiliation
Department of Bioengineering, Rice University, Houston, Texas 77005, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural