1gnp
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X-RAY CRYSTAL STRUCTURE ANALYSIS OF THE CATALYTIC DOMAIN OF THE ONCOGENE PRODUCT P21H-RAS COMPLEXED WITH CAGED GTP AND MANT DGPPNHP
OverviewOverview
The X-ray structures of the 1:1 complexes formed between p21H-ras, (residues 1 to 166) and the nucleotides P3-1-(2-nitrophenyl)ethyl, guanosine triphosphate ("caged GTP"; pure R- and S-diastereomers) and, 3'-O-(N-methylanthraniloyl)-2'-deoxyguanosine 5'-(beta, gamma-imido)-triphosphate ("mant dG-ppNHp"), have been refined to an, R-factor of 21.4% (R-caged GTP, 1.85 A resolution), 18.9% (S-caged GTP, 2.5 A resolution) and 17.6% (mant dGppNHp, 2.7 A resolution), respectively. Details of the structure determination, refinement and the, structures themselves are presented. The overall structures of the, complexes are identical in terms of the general organization of their, secondary structure elements and are also identical to that reported for, the analogous complex of p21H-ras with GppNHp. The binding of the GTP part, is not significantly affected by the additional aromatic group (cage and, mant, respectively) in contrast to the original observation on p21:caged, GTP using the racemic mixture of R- and S-caged GTP. The main differences, in the structures are observed in the region of loop L2 (residues Glu31 to, Thr35) where the additional aromatic group attached to the nucleotide, comes very close to the side-chain of Tyr32, including backbone, displacements of 2.6 A, 2.2 A and 0.3 A for the residues from Glu31 to, Thr35 for R-caged, S-caged GTP and mant dGppNHp, respectively. The refined, structures provide additional data for the design of new nucleotide, analogs and the importance of their stereochemistry as well as for the, design of new mutant forms of p21H-ras for further biochemical, investigations. The binding mode of mant dGppNHp reveals significant, features for the understanding of the fluorescence signals observed in, solution.
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
1GNP is a Single protein structure of sequence from Homo sapiens with MG and AGN as ligands. Full crystallographic information is available from OCA.
ReferenceReference
X-ray crystal structure analysis of the catalytic domain of the oncogene product p21H-ras complexed with caged GTP and mant dGppNHp., Scheidig AJ, Franken SM, Corrie JE, Reid GP, Wittinghofer A, Pai EF, Goody RS, J Mol Biol. 1995 Oct 13;253(1):132-50. PMID:7473708
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