Bioactive conformation of Arg-Gly-Asp by x-ray data analyses and molecular mechanics.
Analysis of well resolved x-ray crystal structure data of proteins (Brookhaven protein data bank) has been combined with molecular mechanics methods using MM2, to determine possible bioactive conformations for the sequence Arg-Gly-Asp, which is believed to be involved in interactions of adhesive proteins with the glycoprotein complexes on activated platelets. In spite of the very flexible nature of this tripeptide fragment, only three general classes of structures were obtained. In one of them, the guanidinium and carboxylate moieties are in hydrogen-bonding proximity, while in the other they are separated by distances of greater than 8 A. Recent literature on the binding affinity of some rigid platelet-aggregation inhibitors seems to support the latter class of structures to correspond to the bioactive conformation.
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Searle Research and Development Division of G.D. Searle and Co., Skokie, IL 60077.
D000595:Amino Acid Sequence; D003198:Computer Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid