Linked Life Data

17080222

Source:http://linkedlifedata.com/resource/pubmed/id/17080222

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-11-2
pubmed:abstractText
Although discovered as potent inhibitors of a (IIb) ss (3) -mediated platelet aggregation, snake venom disintegrins are now known to bind to other integrins according to different degrees of potency and specificity. More recently, homologues of the disintegrinlike loop have been found as a discrete domain in the ADAM family, yet the potency and specificity of each of these domains in terms of integrin binding is relatively unknown. In this present study, we have selected the disintegrin-like domain (dd) of ADAM-15 (designated as ddADAM-15), the only RGD containing domain in the ADAM family, for a structure/function study. Experimentally, the ddADAM-15 and a number of mutants in which the RGD-containing loop was substituted by cognate regions from ADAM-2, -12 and -19 were tested in terms of integrin-binding activity. For comparison with ADAM-15, an additional mutant (dd (den) ADAM-15) was designed based upon the RGD-containing loop of snake venom dendroaspin, a disintegrin-like integrin antagonist. The results showed that ddADAM-15 is an inhibitor of platelet aggregation, though with less potency than dd (den) ADAM-15. None of the other mutants exhibited significant inhibition of platelet aggregation. ddADAM-15 was found to have higher binding ability for a (2) ss (1) and a (9) ss (1) than the ADAM-2 derived mutant which appeared to be more selective for a (V) ss (3) and a (4) ss (1) than either ddADAM-15 or its ADAM-19 based mutant. The integrin-binding properties of ddADAM-15 were completely abolished by point mutation within the RGD motif (R (64) GD ? A (64) GD). These results suggest a more subtle contribution of this loop sequence to defining the functionality of the ADAMs compared to dendroaspin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
642-51
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Integrin binding characteristics of the disintegrin-like domain of ADAM-15.
pubmed:affiliation
Thrombosis Research Institute, Manresa Road, London, SW3 6LR, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't