821p

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{{STRUCTURE_821p| PDB=821p | SCENE= }}
{{STRUCTURE_821p| PDB=821p | SCENE= }}
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'''THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS'''
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===THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS===
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==Overview==
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The three-dimensional structures and biochemical properties of two mutants of the G-domain (residues 1-166) of p21H-ras, p21 (G12D) and p21 (G12P), have been determined in the triphosphate-bound form using guanosine 5'-(beta,gamma-imido)triphosphate (GppNHp). They correspond to the most frequent oncogenic and the only nononcogenic mutation of Gly-12, respectively. The G12D mutation is the only mutant analyzed so far that crystallizes in a space group different from wild type, and the atomic model of the protein shows the most drastic changes of structure around the active site as compared to wild-type p21. This is due to the interactions of the aspartic acid side chain with Tyr-32, Gln-61, and the gamma-phosphate, which result in reduced mobility of these structural elements. The interaction between the carboxylate group of Asp-12 and the gamma-phosphate is mediated by a shared proton, which we show by 31P NMR measurements to exist in solution as well. The structure of p21 (G12P) is remarkably similar to that of wild-type p21 in the active site, including the position of the nucleophilic water. The pyrrolidine ring of Pro-12 points outward and seems to be responsible for the weaker affinity toward GAP (GTPase-activating protein) and the failure of GAP to stimulate GTP hydrolysis.
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(as it appears on PubMed at http://www.pubmed.gov), where 8357792 is the PubMed ID number.
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{{ABSTRACT_PUBMED_8357792}}
==About this Structure==
==About this Structure==
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[[Category: Wittinghofer, A.]]
[[Category: Wittinghofer, A.]]
[[Category: Oncogene protein]]
[[Category: Oncogene protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Jul 11 12:52:17 2008''

Revision as of 09:52, 11 July 2008

Image:821p.png

Template:STRUCTURE 821p

THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS

Template:ABSTRACT PUBMED 8357792

About this Structure

821P is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras., Franken SM, Scheidig AJ, Krengel U, Rensland H, Lautwein A, Geyer M, Scheffzek K, Goody RS, Kalbitzer HR, Pai EF, et al., Biochemistry. 1993 Aug 24;32(33):8411-20. PMID:8357792

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