1iaq
From Proteopedia
(New page: 200px<br /> <applet load="1iaq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1iaq, resolution 2.9Å" /> '''C-H-RAS P21 PROTEIN ...) |
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caption="1iaq, resolution 2.9Å" /> | caption="1iaq, resolution 2.9Å" /> | ||
'''C-H-RAS P21 PROTEIN MUTANT WITH THR 35 REPLACED BY SER (T35S) COMPLEXED WITH GUANOSINE-5'-[B,G-IMIDO] TRIPHOSPHATE'''<br /> | '''C-H-RAS P21 PROTEIN MUTANT WITH THR 35 REPLACED BY SER (T35S) COMPLEXED WITH GUANOSINE-5'-[B,G-IMIDO] TRIPHOSPHATE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IAQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1IAQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IAQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: proto-oncogene]] | [[Category: proto-oncogene]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:00:30 2008'' |
Revision as of 14:00, 15 February 2008
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C-H-RAS P21 PROTEIN MUTANT WITH THR 35 REPLACED BY SER (T35S) COMPLEXED WITH GUANOSINE-5'-[B,G-IMIDO] TRIPHOSPHATE
Contents |
Overview
We have investigated the dynamic properties of the switch I region of the, GTP-binding protein Ras by using mutants of Thr-35, an invariant residue, necessary for the switch function. Here we show that these mutants, previously used as partial loss-of-function mutations in cell-based, assays, have a reduced affinity to Ras effector proteins without Thr-35, being involved in any interaction. The structure of Ras(T35S)(.)GppNHp was, determined by x-ray crystallography. Whereas the overall structure is very, similar to wildtype, residues from switch I are completely invisible, indicating that the effector loop region is highly mobile. (31)P-NMR data, had indicated an equilibrium between two rapidly interconverting, conformations, one of which (state 2) corresponds to the structure found, in the complex with the effectors. (31)P-NMR spectra of Ras mutants (T35S), and (T35A) in the GppNHp form show that the equilibrium is shifted such, that they occur predominantly in the nonbinding conformation (state 1). On, addition of Ras effectors, Ras(T35S) but not Ras(T35A) shift to positions, corresponding to the binding conformation. The structural data were, correlated with kinetic experiments that show two-step binding reaction of, wild-type and (T35S)Ras with effectors requires the existence of a, rate-limiting isomerization step, which is not observed with T35A. The, results indicate that minor changes in the switch region, such as removing, the side chain methyl group of Thr-35, drastically affect dynamic behavior, and, in turn, interaction with effectors. The dynamics of the switch I, region appear to be responsible for the conservation of this threonine, residue in GTP-binding proteins.
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
1IAQ is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Dynamic properties of the Ras switch I region and its importance for binding to effectors., Spoerner M, Herrmann C, Vetter IR, Kalbitzer HR, Wittinghofer A, Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4944-9. PMID:11320243
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