ISSN:
1573-4951
Keywords:
cation-π interactions
;
integrin
;
KGD
;
molecular dynamics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Disintegrins constitute a class of small proteins that inhibit platelet aggregation by binding to the fibrinogen receptor, also referred to as integrin αIIbβ3. Contrarily to other disintegrins that bind to a series of integrins via their Arg-Gly-Asp domain, the recognition site of barbourin contains a Lys-Gly-Asp sequence that ensures its specificity towards αIIbβ3. In this article, a three-dimensional model of barbourin is proposed using homology modeling and large-scale molecular dynamics simulations. The conformations of the Lys-Gly-Asp sequence of barbourin are analyzed and compared to those of peptidomimetics that exhibit similar specificity towards αIIbβ3. The tryptophan residue following the Lys-Gly-Asp sequence of the binding domain is shown to play a crucial role in the biological activity and the specificity of barbourin. Our results suggest that this disintegrin anchors to the binding pocket of the γ-chain of fibrinogen rather than to those of the Arg-Gly-Asp sequence.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008182011731
Permalink
