View source for 8cnj


==HRas(1-166) in complex with GDP and BeF3-==
<StructureSection load='8cnj' size='340' side='right'caption='[[8cnj]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8cnj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CNJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cnj OCA], [https://pdbe.org/8cnj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cnj RCSB], [https://www.ebi.ac.uk/pdbsum/8cnj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cnj ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tyrosine phosphorylation on Ras by Src kinase is known to uncouple Ras from upstream regulation and downstream communication. However, the mechanisms by which phosphorylation modulates these interactions have not been detailed. Here, the major mono-phosphorylation level on tyrosine64 is quantified by (31)P NMR and mutagenesis. Crystal structures of unphosphorylated and tyrosine64-phosphorylated Ras in complex with a BeF(3)(-) ground state analogue reveal "closed" Ras conformations very different from those of the "open" conformations previously observed for non-hydrolysable GTP analogue structures of Ras. They deliver new mechanistic and conformational insights into intrinsic GTP hydrolysis. Phosphorylation of tyrosine64 delivers conformational changes distant from the active site, showing why phosphorylated Ras has reduced affinity to its downstream effector Raf. (19)F NMR provides evidence for changes in the intrinsic GTPase and nucleotide exchange rate and identifies the concurrent presence of a major "closed" conformation alongside a minor yet functionally important "open" conformation at the ground state of Ras. This study expands the application of metal fluoride complexes in revealing major and minor conformational changes of dynamic and modified Ras proteins.

Far-reaching effects of tyrosine64 phosphorylation on Ras revealed with BeF(3)(-) complexes.,Baumann P, Jin Y Commun Chem. 2024 Jan 31;7(1):19. doi: 10.1038/s42004-024-01105-6. PMID:38297137<ref>PMID:38297137</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8cnj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baumann P]]
[[Category: Jin Y]]