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'''THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY'''<br /> | '''THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1CRR 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 GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1CRR 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=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CRR OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: oncogene protein]] | [[Category: oncogene protein]] | ||
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THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY
OverviewOverview
A high-resolution solution structure of the GDP form of a truncated, version of the ras p21 protein (residues 1-166) has been determined using, NMR spectroscopy. Ras p21 is the product of the human ras protooncogene, and a member of a ubiquitous eukaryotic gene family which is highly, conserved in evolution. A virtually complete assignment (13C, 15N, and, 1H), including stereospecific assignments of 54 C beta methylene protons, and 10 C gamma methyl protons of valine residues, was obtained by analysis, of three- and four-dimensional (3D and 4D) heteronuclear NMR spectra using, a newly developed 3D/4D version of the ANSIG software. A total of 40, converged structures were computed from 3369 experimental restraints, consisting of 3,167 nuclear Overhauser effect (NOE) derived distances, 14, phi and 54 chi 1 torsion angle restraints, 109 hydrogen bond distance, restraints, and an additional 25 restraints derived from literature data, defining interactions between the GDP ligand, the magnesium ion, and the, protein. The structure in the region of residues 58-66 (loop L4), and to a, lesser degree residues 30-38 (loop L2), is ill-defined. Analysis of the, dynamics of the backbone 15N nuclei in the protein showed that residues, within the regions 58-66, 107-109, and, to a lesser degree, 30-38 are, dynamically mobile on the nanosecond time scale. The root mean square, (rms) deviations between the 40 solution structures and the mean atomic, coordinates are 0.78 A for the backbone heavy atoms and 1.29 A for all, non-hydrogen atoms if all residues (1-166) are included in the analysis., If residues 30-38 and residues 58-66 are excluded from the analysis, the, rms deviations are reduced to 0.55 and 1.00 A, respectively. The structure, was compared to the most highly refined X-ray crystal structure of ras, p21.GDP (1-189) [Milburn, M. V., Tong, L., de Vos, A. M., Brunger, A. T., Yamaizumi, Z., Nishimura, S., & Kim, S.-H. (1990) Science 24, 939-945]., The structures are very similar except in the regions found to be mobile, by NMR spectroscopy. In addition, the second alpha-helix (helix-2) has a, slightly different orientation. The rms deviation between the average of, the solution structures and the X-ray crystal structure is 0.94 A for the, backbone heavy atoms if residues 31-37 and residues 59-73 are excluded, from the analysis.
DiseaseDisease
Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]
About this StructureAbout this Structure
1CRR is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure and dynamics of ras p21.GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy., Kraulis PJ, Domaille PJ, Campbell-Burk SL, Van Aken T, Laue ED, Biochemistry. 1994 Mar 29;33(12):3515-31. PMID:8142349
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