Structural analysis of the KGD sequence loop of barbourin, an alphaIIbbeta3-specific disintegrin

J Comput Aided Mol Des. 2000 May;14(4):317-27. doi: 10.1023/a:1008182011731.


Disintegrins constitute a class of small proteins that inhibit platelet aggregation by binding to the fibrinogen receptor, also referred to as integrin alphaIIbbeta3. 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 alphaIIbbeta3. 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 alphaIIbbeta3. 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 gamma-chain of fibrinogen rather than to those of the Arg-Gly-Asp sequence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Computer Simulation
  • Crotalid Venoms / chemistry*
  • Crotalid Venoms / genetics
  • Disintegrins / chemistry*
  • Disintegrins / genetics
  • Drug Design
  • Humans
  • In Vitro Techniques
  • Models, Molecular
  • Molecular Sequence Data
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Thermodynamics


  • Crotalid Venoms
  • Disintegrins
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • barbourin