6n47

<table><tr><td colspan='2'>[[6n47]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat], [http://en.wikipedia.org/wiki/Chick Chick] and [http://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N47 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=KB4:4-(2-chloropyrido[3,2-d]pyrimidin-4-yl)-7-methoxy-3,4-dihydroquinoxalin-2(1H)-one'>KB4</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TUBA1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG]), TUBB2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), Stmn4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), TTL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6n47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n47 OCA], [http://pdbe.org/6n47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n47 RCSB], [http://www.ebi.ac.uk/pdbsum/6n47 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n47 ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/TBA1B_PIG TBA1B_PIG]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [[http://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref> [[http://www.uniprot.org/uniprot/TBB2B_BOVIN TBB2B_BOVIN]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).

Because of its multifaceted role in cellular functions, tubulin is a validated and productive drug target for cancer therapy. While many tubulin inhibitors demonstrate clinical efficacy, they are often limited by the development of multidrug resistance. Therefore, implementation of tubulin inhibitors that can overcome resistance could provide significant therapeutic benefits. To optimize our previously reported tubulin inhibitor, 4a, we designed and synthesized two new analogues, SB202 and SB204, based on the crystal structure of 4a in complex with tubulin protein. SB202 and SB204 achieved enhanced binding at the colchicine site in tubulin and also showed improved metabolic stability and antiproliferative potency in vitro. Functional studies confirmed that SB202 and SB204 inhibit tubulin polymerization, arrest cells in the G2/M phase of the cell cycle, interfere with cancer cell migration and proliferation, and enhance apoptotic cascades. When evaluated in vivo, SB202 exhibited antitumor and vascular disrupting action against paclitaxel-resistant mouse xenograft models, strongly suggesting the potential of this scaffold to overcome multidrug resistance for cancer therapy.

 

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== References ==

[[Category: Bovin]]

[[Category: Buffalo rat]]

[[Category: Chick]]

[[Category: Pig]]

[[Category: Arnst, K]]

[[Category: Banerjee, S]]

[[Category: Li, W]]

[[Category: Miller, D]]

[[Category: Wang, Y]]

[[Category: Tubulin]]