View source for 2evw


==Crystal structure analysis of a fluorescent form of H-Ras p21 in complex with R-caged GTP==
<StructureSection load='2evw' size='340' side='right'caption='[[2evw]], [[Resolution|resolution]] 1.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2evw]] is a 1 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=2EVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EVW 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]] 1.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAG:GUANOSINE+5-TRIPHOSPHATE+P3-[1-(2-NITROPHENYL)ETHYL+ESTER]'>CAG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=XY2:N,N-DIMETHYL-N-(ACETYL)-N-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)ETHYLENEDIAMINE'>XY2</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=2evw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2evw OCA], [https://pdbe.org/2evw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2evw RCSB], [https://www.ebi.ac.uk/pdbsum/2evw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2evw 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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ev/2evw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2evw ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
We present a new design for a fluorescence microspectrophotometer for use in kinetic crystallography in combination with x-ray diffraction experiments. The FLUMIX device (Fluorescence spectroscopy to monitor intermediates in x-ray crystallography) is built for 0 degrees fluorescence detection, which has several advantages in comparison to a conventional fluorometer with 90 degrees design. Due to the reduced spatial requirements and the need for only one objective, the system is highly versatile, easy to handle, and can be used for many different applications. In combination with a conventional stereomicroscope, fluorescence measurements or reaction initiation can be performed directly in a hanging drop crystallization setup. The FLUMIX device can be combined with most x-ray sources, normally without the need of a specialized mechanical support. As a biological model system, we have used H-Ras p21 with an artificially introduced photo-labile GTP precursor (caged GTP) and a covalently attached fluorophore (IANBD amide). Using the FLUMIX system, detailed information about the state of photolyzed crystals of the modified H-Ras p21 (p21(mod)) could be obtained. Measurements in combination with a synchrotron beamline showed significant fluorescence changes in p21(mod) crystals even within a few seconds of x-ray exposure at 100 K.

A newly designed microspectrofluorometer for kinetic studies on protein crystals in combination with x-ray diffraction.,Klink BU, Goody RS, Scheidig AJ Biophys J. 2006 Aug 1;91(3):981-92. Epub 2006 May 12. PMID:16698776<ref>PMID:16698776</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2evw" style="background-color:#fffaf0;"></div>

==See Also==
*[[GTPase Hras 3D structures|GTPase Hras 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Klink BU]]