421p

From Proteopedia

Revision as of 15:44, 15 February 2008

THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES

Overview

The X-ray structures of the guanine nucleotide binding domains (amino, acids 1-166) of five mutants of the H-ras oncogene product p21 were, determined. The mutations described are Gly-12----Arg, Gly-12----Val, Gln-61----His, Gln-61----Leu, which are all oncogenic, and the effector, region mutant Asp-38----Glu. The resolutions of the crystal structures, range from 2.0 to 2.6 A. Cellular and mutant p21 proteins are almost, identical, and the only significant differences are seen in loop L4 and in, the vicinity of the gamma-phosphate. For the Gly-12 mutants the larger, side chains interfere with GTP binding and/or hydrolysis. Gln-61 in, cellular p21 adopts a conformation where it is able to catalyze GTP, hydrolysis. This conformation has not been found for the mutants of, Gln-61. Furthermore, Leu-61 cannot activate the nucleophilic water because, of the chemical nature of its side chain. The D38E mutation preserves its, ability to bind GAP.

Disease

Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]

About this Structure

421P is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules., Krengel U, Schlichting I, Scherer A, Schumann R, Frech M, John J, Kabsch W, Pai EF, Wittinghofer A, Cell. 1990 Aug 10;62(3):539-48. PMID:2199064

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