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6o61

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Revision as of 07:01, 31 July 2019

Tubulin-RB3_SLD-TTL in complex with compound ABI-231

Structural highlights

6o61 is a 6 chain structure with sequence from Chick, Human and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	6o5m, 6o5n
Gene:	STMN4 (HUMAN), TTL (CHICK)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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. [STMN4_HUMAN] Exhibits microtubule-destabilizing activity. [A0A287AGU7_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.[RuleBase:RU000352][SAAS:SAAS00031082]

Publication Abstract from PubMed

ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clinical trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship (SAR) studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogs, most notably 10ab and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved molecular interactions to the colchicine site. In vitro, biological studies showed that new ABI-231 analogs disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analog 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models, but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacological screening suggested that 10bb has a low risk of potential off-target function.

Structure guided design, synthesis, and biological evaluation of 2-(1H-Indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) Methanone (ABI-231) analogs targeting the colchicine binding site in tubulin.,Wang Q, Arnst K, Wang Y, Kumar GK, Ma D, White SW, Miller DD, Li W, Li W J Med Chem. 2019 Jun 28. doi: 10.1021/acs.jmedchem.9b00706. PMID:31251599^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang Q, Arnst K, Wang Y, Kumar GK, Ma D, White SW, Miller DD, Li W, Li W. Structure guided design, synthesis, and biological evaluation of 2-(1H-Indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) Methanone (ABI-231) analogs targeting the colchicine binding site in tubulin. J Med Chem. 2019 Jun 28. doi: 10.1021/acs.jmedchem.9b00706. PMID:31251599 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00706

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6o61"

@@ Line 3: / Line 3: @@
 <StructureSection load='6o61' size='340' side='right'caption='[[6o61]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6o61]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O61 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O61 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6o61]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick], [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O61 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O61 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=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=KUM:[2-(1H-indol-3-yl)-1H-imidazol-5-yl](3,4,5-trimethoxyphenyl)methanone'>KUM</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6o5m|6o5m]], [[6o5n|6o5n]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STMN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 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=6o61 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o61 OCA], [http://pdbe.org/6o61 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o61 RCSB], [http://www.ebi.ac.uk/pdbsum/6o61 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o61 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Chick]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Sus scrofa]]

6o61

From Proteopedia

Revision as of 07:01, 31 July 2019

Tubulin-RB3_SLD-TTL in complex with compound ABI-231

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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