4nyi: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4nyi]] is a 3 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=4NYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYI FirstGlance]. <br>
<table><tr><td colspan='2'>[[4nyi]] is a 3 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=4NYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PX:N-{1-[(5-METHYL-1H-INDOL-3-YL)METHYL]PIPERIDIN-4-YL}-L-TRYPTOPHANAMIDE'>2PX</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9612&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PX:N-{1-[(5-METHYL-1H-INDOL-3-YL)METHYL]PIPERIDIN-4-YL}-L-TRYPTOPHANAMIDE'>2PX</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4nyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyi OCA], [https://pdbe.org/4nyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nyi RCSB], [https://www.ebi.ac.uk/pdbsum/4nyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyi ProSAT]</span></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=4nyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyi OCA], [https://pdbe.org/4nyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nyi RCSB], [https://www.ebi.ac.uk/pdbsum/4nyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyi ProSAT]</span></td></tr>
</table>
</table>
Line 11: Line 12:
== Function ==
== 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>  
[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 ==
Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in approximately 30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.
Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.,Burns MC, Sun Q, Daniels RN, Camper D, Kennedy JP, Phan J, Olejniczak ET, Lee T, Waterson AG, Rossanese OW, Fesik SW Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3401-6. doi: 10.1073/pnas.1315798111., Epub 2014 Feb 18. PMID:24550516<ref>PMID:24550516</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4nyi" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[GTPase Hras 3D structures|GTPase Hras 3D structures]]
*[[GTPase Hras 3D structures|GTPase Hras 3D structures]]
*[[Son of sevenless|Son of sevenless]]
*[[Son of sevenless 3D structures|Son of sevenless 3D structures]]
== References ==
== References ==
<references/>
<references/>
Retrieved from "https://proteopedia.org/4nyi"