1iaq
From Proteopedia
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| - | [[Image:1iaq.jpg|left|200px]] | + | [[Image:1iaq.jpg|left|200px]] |
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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''' | + | {{Structure |
| + | |PDB= 1iaq |SIZE=350|CAPTION= <scene name='initialview01'>1iaq</scene>, resolution 2.9Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER'>GNP</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= HRAS OR HRAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''C-H-RAS P21 PROTEIN MUTANT WITH THR 35 REPLACED BY SER (T35S) COMPLEXED WITH GUANOSINE-5'-[B,G-IMIDO] TRIPHOSPHATE''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IAQ is a [ | + | 1IAQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IAQ OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11320243 11320243] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: proto-oncogene]] | [[Category: proto-oncogene]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:47:50 2008'' |
Revision as of 09:47, 20 March 2008
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| , resolution 2.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | HRAS OR HRAS1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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