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  Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras

Franken, S. M., Scheidig, A. J., Krengel, U., Rensland, H., Lautwein, A., Geyer, M., et al. (1993). Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras. Biochemistry, 32(33), 8411-8420. doi:10.1021/bi00084a005.

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 Creators:
Franken, Sybille M., Author
Scheidig, Axel J., Author
Krengel, Ute1, Author           
Rensland, Hans, Author
Lautwein, Alfred, Author
Geyer, Matthias1, Author           
Scheffzek, Klaus1, Author           
Goody, Roger S.1, Author           
Kalbitzer, Hans Robert1, Author           
Pai, Emil F., Author
Wittinghofer, Alfred1, Author           
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1Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497712              

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 Abstract: 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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Language(s): eng - English
 Dates: 1992-12-281993-04-011993-08-24
 Publication Status: Issued
 Pages: 10
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 Rev. Type: Peer
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Title: Biochemistry
Source Genre: Journal
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Publ. Info: Columbus, Ohio : American Chemical Society
Pages: - Volume / Issue: 32 (33) Sequence Number: - Start / End Page: 8411 - 8420 Identifier: ISSN: 0006-2960
CoNE: https://pure.mpg.de/cone/journals/resource/954925384103