Linked Life Data

20925690

Source:http://linkedlifedata.com/resource/pubmed/id/20925690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-10-7
pubmed:abstractText
Heat shock protein 90 (Hsp90) is a prime target for antitumor therapies. The information obtained by molecular dynamics (MD) simulations is combined with NMR data to provide a cross-validated atomic resolution model of the complementary interactions of heat shock protein 90 with a peptidic (shepherdin) and a non-peptidic (5-aminoimidazole-4-carboxamide-1-?-d-ribofuranoside, AICAR) inhibitor, showing antiproliferative and proapoptotic activity in multiple tumor cell lines. This approach highlights the relevant role of imidazolic moiety in the interaction of both antagonist molecules. In 5-aminoimidazole-4-carboxamide-1-?-d-ribofuranoside bound state, one conformation of those present in solution is selected, where imidazolic, H4 and H5 protons have a key role in defining a non-polar region contacting heat shock protein 90 surface. The dynamic equilibrium between N-type and S-type puckered forms of 5-aminoimidazole-4-carboxamide-1-?-d-ribofuranoside moiety is shown to be functional to inhibitor binding. The first experimental structural data on these inhibitors are presented and discussed as hints for future design of improved molecules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1747-0285
pubmed:author
pubmed:copyrightInfo
© 2010 John Wiley & Sons A/S.
pubmed:issnType
Electronic
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
382-91
pubmed:dateRevised
2011-11-1
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Combined in silico and experimental approach for drug design: the binding mode of peptidic and non-peptidic inhibitors to hsp90 N-terminal domain.
pubmed:affiliation
Istituto per lo Studio Delle Macromolecole, Consiglio Nazionale delle Ricerche, Milano, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural