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4fk3: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4fk3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3c4d 3c4d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FK3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4fk3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3c4d 3c4d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FK3 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=325:N-{2,4-DIFLUORO-3-[(5-PYRIDIN-3-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)CARBONYL]PHENYL}ETHANESULFONAMIDE'>325</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]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=325:N-{2,4-DIFLUORO-3-[(5-PYRIDIN-3-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)CARBONYL]PHENYL}ETHANESULFONAMIDE'>325</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=4fk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fk3 OCA], [https://pdbe.org/4fk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fk3 RCSB], [https://www.ebi.ac.uk/pdbsum/4fk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fk3 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=4fk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fk3 OCA], [https://pdbe.org/4fk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fk3 RCSB], [https://www.ebi.ac.uk/pdbsum/4fk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fk3 ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BRAF(V600E) is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting "active" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf(V600E) kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf(V600E)-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. In B-Raf(V600E)-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf(V600E)-driven tumors.
Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity.,Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6. Epub 2008 Feb 19. PMID:18287029<ref>PMID:18287029</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4fk3" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

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