Linked Life Data

16784459

Source:http://linkedlifedata.com/resource/pubmed/id/16784459

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-6-20
pubmed:abstractText
The finding that the chemokine receptor CXCR4 is involved in T-cell HIV entry has encouraged the development of antiretroviral drugs targeting this receptor. Additional evidence that CXCR4 plays a crucial role in both angiogenesis and metastasis provides further motivation for the development of a CXCR4 inhibitor for therapeutic applications in oncology. To facilitate the design of such ligands, we have investigated the possible binding modes for cyclopentapeptide CXCR4 antagonists by docking 11 high/medium affinity cyclopentapeptides to a developed three-dimensional model of the CXCR4 G-protein-coupled receptor's transmembrane region. These ligands, expected to bind in the same mode to the receptor, were docked in the previously deduced receptor-bound conformation [Våbenøet al., in press; doi 10.1002/bip.20508]. Ligand-receptor complexes were generated using an automated docking procedure that allowed ligand flexibility. By comparing the resulting ligand poses, only two binding modes common for all 11 compounds were identified. Inspection of these two ligand-receptor complexes identified several CXCR4 contact residues shown by mutation to be interaction sites for ligands and important for HIV gp120 binding. Thus, the results provide further insight into the mechanism by which these cyclopentapeptides block HIV entry as well as a basis for rational design of CXCR4 mutants to map potential contacts with small peptide ligands.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1747-0277
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
346-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Insight into the binding mode for cyclopentapeptide antagonists of the CXCR4 receptor.
pubmed:affiliation
Department of Biochemistry and Molecular Biophysics, Center for Computational Biology, Washington University School of Medicine, 700 South Euclid Avenue, St Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural