Cysteine pairing in the glycoprotein IIbIIIa antagonist kistrin using NMR, chemical analysis, and structure calculations.
The pairing of the cysteines in disulfide bonds was investigated for the 68-residue RGD-containing protein kistrin, a potent antagonist of the integrin GP IIbIIIa and an inhibitor of platelet aggregation. Kistrin belongs to a family of homologous proteins found in snake venoms termed disintegrins, all of which have a cysteine content. The disulfide pairing of the 12 cysteines was investigated by chemical analysis, NMR spectroscopy, and distance geometry calculations. The data show that the disulfide pairs are 4-19, 6-14, 13-36, 27-33, 32-57, and 45-64. The various means for assigning the disulfide bonds are described, and the results are compared with the cysteine pairings reported for other disintegrin proteins.
Adler
M
M
Berlex Laboratories, Inc., Morristown, New Jersey 07927.
Carter
P
P
Lazarus
R A
RA
Wagner
G
G
D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003435:Crotalid Venoms / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D010450:Endopeptidases / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D017433:Protein Structure, Secondary; D014757:Viper Venoms / Q000737:chemistry
D003435:Crotalid Venoms; D004220:Disulfides; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D014757:Viper Venoms; C057986:echistatin; C067623:kistrin; D010450:Endopeptidases; D003545:Cysteine