2j06: Difference between revisions

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[[Image:2j06.jpg|left|200px]]<br /><applet load="2j06" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2j06, resolution 1.80&Aring;" />
'''CRYSTAL STRUCTURE OF THE RASGAP SH3 DOMAIN AT 1.8 ANGSTROM RESOLUTION'''<br />


==Overview==
==Crystal structure of the RasGAP SH3 domain at 1.8 Angstrom resolution==
X-ray structures of two crystal forms of the Src homology 3 domain (SH3), of the Ras GTPase activating protein (RasGAP) were determined at 1.5 and, 1.8A resolution. The overall structure comprises a single domain with two, tightly packed beta-sheets linked by a short helical segment. An important, motif for peptide binding in other SH3 domains is not conserved in RasGAP., The RasGAP SH3 domain forms dimers in the crystal structures, which may, provide new functional insight. The dimer interface involves residues also, present in a peptide previously identified as an apoptotic sensitizer of, tumor cells.
<StructureSection load='2j06' size='340' side='right'caption='[[2j06]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2j06]] 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=2J06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J06 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2j06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j06 OCA], [https://pdbe.org/2j06 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j06 RCSB], [https://www.ebi.ac.uk/pdbsum/2j06 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j06 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RASA1_HUMAN RASA1_HUMAN] Note=Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas.  Defects in RASA1 are the cause of capillary malformation-arteriovenous malformation (CMAVM) [MIM:[https://omim.org/entry/608354 608354]. CMAVM is a disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome.<ref>PMID:14639529</ref>  Defects in RASA1 are a cause of Parkes Weber syndrome (PKWS) [MIM:[https://omim.org/entry/608355 608355]. PKWS is a disorder characterized by a cutaneous flush with underlying multiple micro-arteriovenous fistulas, in association with soft tissue and skeletal hypertrophy of the affected limb.
== Function ==
[https://www.uniprot.org/uniprot/RASA1_HUMAN RASA1_HUMAN] Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1.<ref>PMID:8360177</ref> <ref>PMID:11389730</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/j0/2j06_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2j06 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
X-ray structures of two crystal forms of the Src homology 3 domain (SH3) of the Ras GTPase activating protein (RasGAP) were determined at 1.5 and 1.8A resolution. The overall structure comprises a single domain with two tightly packed beta-sheets linked by a short helical segment. An important motif for peptide binding in other SH3 domains is not conserved in RasGAP. The RasGAP SH3 domain forms dimers in the crystal structures, which may provide new functional insight. The dimer interface involves residues also present in a peptide previously identified as an apoptotic sensitizer of tumor cells.


==Disease==
High resolution crystal structures of the p120 RasGAP SH3 domain.,Ross B, Kristensen O, Favre D, Walicki J, Kastrup JS, Widmann C, Gajhede M Biochem Biophys Res Commun. 2007 Feb 9;353(2):463-8. Epub 2006 Dec 18. PMID:17188236<ref>PMID:17188236</ref>
Known diseases associated with this structure: Basal cell carcinoma, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139150 139150]], Capillary malformation-arteriovenous malformation OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139150 139150]], Parkes Weber syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139150 139150]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2J06 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=2J06 OCA].
</div>
<div class="pdbe-citations 2j06" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
High resolution crystal structures of the p120 RasGAP SH3 domain., Ross B, Kristensen O, Favre D, Walicki J, Kastrup JS, Widmann C, Gajhede M, Biochem Biophys Res Commun. 2007 Feb 9;353(2):463-8. Epub 2006 Dec 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17188236 17188236]
*[[Ras GTPase activating protein|Ras GTPase activating protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Gajhede, M.]]
[[Category: Gajhede M]]
[[Category: Kristensen, O.]]
[[Category: Kristensen O]]
[[Category: Ross, B.]]
[[Category: Ross B]]
[[Category: disease mutation]]
[[Category: gtpase activating protein]]
[[Category: gtpase activation]]
[[Category: phosphorylation]]
[[Category: proto-oncogene]]
[[Category: ras signaling pathway]]
[[Category: sh2 domain]]
[[Category: sh3 domain]]
[[Category: signal transduction]]
[[Category: src homology 3]]
 
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