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Determination of the structure of two novel echistatin variants and comparison of the ability of echistatin variants to inhibit aggregation of platelets from different species.
- Source :
-
The Biochemical journal [Biochem J] 1995 Jan 15; Vol. 305 ( Pt 2), pp. 513-20. - Publication Year :
- 1995
-
Abstract
- Two new variants of short disintegrins were purified from the venom of Echis carinatus leakeyi and named echistatin beta and gamma. These proteins were found to be about 85% similar in amino acid sequence to echistatin alpha which has been well studied. The disulphide pattern of echistatin gamma appeared to be identical with that of echistatin alpha. They all contain the adhesive recognition sequence Arg-Gly-Asp (RGD) but inhibit the aggregation of platelets from human and other mammals with different potencies. Echistatin beta and alpha are far more effective on platelets from humans and guinea pigs than those from rabbits and rats whereas echistatin gamma is less discriminating of the platelets of the species tested. This species-dependent platelet sensitivity to echistatin beta and gamma could be attributed to the variations in residues 15, 21, 22 and 27, which are close to or within the RGD loop, rather than to the C-terminal variations after residue 46. Taking advantage of the presence of methionine residues flanking both sides of the ARGDDM motif in echistatin gamma, we deleted this hexapeptide by CNBr cleavage to produce des-(23-28)-echistatin gamma. The modified protein showed c.d. and fluorescent spectra grossly similar to the intact echistatin but its antiplatelet potency decreased more than 200-fold. We thus propose that a favourable conformation of the RGD region is responsible mainly for the high-affinity binding of echistatin to the platelet glycoprotein IIb-IIIa as shown previously for the binding of medium-size disintegrin.
- Subjects :
- Amino Acid Sequence
Animals
Binding, Competitive
Disintegrins
Disulfides chemistry
Dose-Response Relationship, Drug
Fluorescein-5-isothiocyanate metabolism
Guinea Pigs
Humans
Intercellular Signaling Peptides and Proteins
Methionine chemistry
Molecular Sequence Data
Oxidation-Reduction
Peptides metabolism
Peptides pharmacology
Platelet Aggregation Inhibitors pharmacology
Rats
Rats, Sprague-Dawley
Sequence Analysis
Sequence Homology, Amino Acid
Species Specificity
Structure-Activity Relationship
Viper Venoms pharmacology
Peptides chemistry
Platelet Aggregation Inhibitors chemistry
Viper Venoms chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 305 ( Pt 2)
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 7832768
- Full Text :
- https://doi.org/10.1042/bj3050513