[A peptide inhibitor of the binding site of oncoproteins of the p21ras family].
The method of theoretical conformational analysis was used to study the inverse structural problem to determine the amino acid sequence of the peptide molecule capable of inhibiting the site of binding of p21 to cell receptors. At the first stage of the computational experiment, the spatial structure and the conformational possibilities of the binding sites of protein p21 and its cellular receptors were determined. Then the three-dimensional structures of several peptides containing the Arg-Ala-Ala-Glu-Asp site were studied. By varying the number of alanine residues in the adjacent regions of the molecule, the sequence H-Asp1-Ala2-Ala3-Ala4-Arg5-Ala6-Ala7-Glu8-Asp9-Ala10-Ala11--Lys12-QH was chosen, which most adequately simulates the conformational properties of the address fragments of oncoprotein receptors. The peptide-molecule having this primary structure is capable of forming a complex with p21, i.e., blocking the binding site of the oncoprotein by preventing the signal transduction from the oncoprotein to the cell, thereby breaking the cycle of the carcinogenic process.
Mzareulov
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D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D010455:Peptides; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)