Format

Send to:

Choose Destination
See comment in PubMed Commons below

Identification by Site-directed Mutagenesis of Amino Acid Residues Flanking RGD Motifs of Snake Venom Disintegrins for Their Structure and Function.

Author information

  • 1Life Science Institute, Henan Normal University, Xinxiang 453002, China. xucunshuan@yahoo.com

Abstract

In order to demonstrate that the amino acid residues flanking the RGD sequence were important for inhibiting the ADP-induced platelet aggregation, we analyzed the role of the amino acid residues in the domain preceding the RGD loop on the activity of disintegrins. Our approach was to develop hybrids between the disintegrins kistrin and elegantin targeting residues in this domain and within the RGD loop. The basic sequence within elegantin KKKR( 44 ) T ( 45 ) I ( 46 ) /A (50)RGDN(54)P(55) was changed by mutagensis to SKAG ( 44 ) T ( 45 ) I ( 46 )/P(50)RGDM(54)P(55) and to SKAG(44)I(46)/P(50)RGDM(54)P(55), thereby resembling the corresponding S(39)RAGT(43)/P(50)RGDM(52)P(53) sequence in kistrin. This changed KKKR(44)T(45)I(46)/A(50)RGDN(54)P(55)right curved arrow SKAG(44)T(45)I(46)/P(50)RGDM(54)P(55) dramatically reduced the activity of elegantin as an inhibitor of platelet aggregation. In contrast, deletion of T(45) (KKKR(44)T(45)I(46)/A(50)RGDN(54)P(55)right curved arrow SKAG(44)T(45)I(46)/P(50)RGDM(54)P(55))increased activity of elegantin as an inhibitor platelet aggregation. It was further shown that their electrophoresis properties were very different. These data highlight the importance of the domain encompassing residues 39--45 and the amimo acid residues flanking the RGD sequence on disintegrin structure-function.

PMID:
12050803
[PubMed - as supplied by publisher]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Shanghai Scientific and Technical Publishers
    Loading ...
    Write to the Help Desk