Linked Life Data

15256703

Source:http://linkedlifedata.com/resource/pubmed/id/15256703

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-7-16
pubmed:abstractText
Human microsomal cytochrome P450s participate in drug metabolism and detoxification. Among them, CYP3A4 is the most important isoform for drug-drug interactions. To gain a better understanding of the active site, a homology model of CYP3A4 was constructed based on the crystallographic coordinates of mammalian CYP2C5. The putative active site is much larger than that of CYP2C5 and is divided into three parts (i.e. a proximal and two distal sites from the heme). Most residues reported to be important for ligand-binding are located in the active site of the model. Moreover, some inhibitors (paclitaxel etc.) docked into the model have complementary shapes to the pocket. Pharmacophore docking of 14 substrates was also performed using Ph4Dock of MOE. Calculated interaction energies showed a moderate correlation with the logarithm of apparent K(m) values. These results suggest that this model is reliable enough to be used in the design of compounds for removing undesirable CYP3A4 inhibition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0009-2363
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
830-5
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Characterization of the CYP3A4 active site by homology modeling.
pubmed:affiliation
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd. Osaka, Japan. Tanaka_Toshimasa@takeda.co.jp
pubmed:publicationType
Journal Article