3kud

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{{Seed}}
 
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[[Image:3kud.png|left|200px]]
 
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==Complex of Ras-GDP with RafRBD(A85K)==
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The line below this paragraph, containing "STRUCTURE_3kud", creates the "Structure Box" on the page.
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<StructureSection load='3kud' size='340' side='right'caption='[[3kud]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3kud]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The March 2016 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Raf Protein Kinases'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2016_3 10.2210/rcsb_pdb/mom_2016_3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KUD FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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{{STRUCTURE_3kud| PDB=3kud | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kud OCA], [https://pdbe.org/3kud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kud RCSB], [https://www.ebi.ac.uk/pdbsum/3kud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kud ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN] Defects in HRAS are the cause of faciocutaneoskeletal syndrome (FCSS) [MIM:[https://omim.org/entry/218040 218040]. A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.<ref>PMID:16170316</ref> <ref>PMID:16329078</ref> <ref>PMID:16443854</ref> <ref>PMID:17054105</ref> <ref>PMID:18247425</ref> <ref>PMID:18039947</ref> <ref>PMID:19995790</ref> Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:[https://omim.org/entry/218040 218040]. CMEMS is a variant of Costello syndrome.<ref>PMID:17412879</ref> Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma (HCTC) [MIM:[https://omim.org/entry/607464 607464]. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms. Note=Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. Defects in HRAS are a cause of susceptibility to bladder cancer (BLC) [MIM:[https://omim.org/entry/109800 109800]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Note=Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC).<ref>PMID:1459726</ref> Defects in HRAS are the cause of Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:[https://omim.org/entry/163200 163200]. A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.<ref>PMID:22683711</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.<ref>PMID:14500341</ref> <ref>PMID:9020151</ref> <ref>PMID:12740440</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ku/3kud_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kud ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch.
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===Complex of Ras-GDP with RafRBD(A85K)===
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What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.,Filchtinski D, Sharabi O, Ruppel A, Vetter IR, Herrmann C, Shifman JM J Mol Biol. 2010 Jun 11;399(3):422-35. Epub 2010 Mar 31. PMID:20361980<ref>PMID:20361980</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3kud" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20361980}}, adds the Publication Abstract to the page
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*[[GTPase Hras 3D structures|GTPase Hras 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20361980 is the PubMed ID number.
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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== References ==
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{{ABSTRACT_PUBMED_20361980}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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3KUD is a 2 chains structure with sequences 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=3KUD OCA].
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==Reference==
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<ref group="xtra">PMID:20361980</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Filchtinski, D.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Herrmann, C.]]
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[[Category: Raf Protein Kinases]]
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[[Category: Rueppel, A.]]
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[[Category: Filchtinski D]]
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[[Category: Sharabi, O.]]
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[[Category: Herrmann C]]
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[[Category: Shifman, J M.]]
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[[Category: Rueppel A]]
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[[Category: Vetter, I R.]]
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[[Category: Sharabi O]]
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[[Category: Gtp binding protein-transferase complex]]
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[[Category: Shifman JM]]
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[[Category: Gtp-binding]]
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[[Category: Vetter IR]]
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[[Category: Nucleotide-binding]]
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[[Category: Proto-oncogene]]
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[[Category: Ras-effector complex]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 1 09:24:59 2010''
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Current revision

Complex of Ras-GDP with RafRBD(A85K)

PDB ID 3kud

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