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5jvd

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Revision as of 11:41, 17 June 2020

Tubulin-TUB092 complex

Structural highlights

5jvd is a 6 chain structure with sequence from Bos taurus, Buffalo rat and Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , ,
Gene:	Stmn4 (Buffalo rat), TTL (CHICK)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TBA1B_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. [STMN4_RAT] Exhibits microtubule-destabilizing activity.^[1] ^[2] ^[3] [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).

Publication Abstract from PubMed

We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is (E)-3-(3-amino-4-methoxyphenyl)-1-(5'-methoxy-3',4'-methylendioxyphenyl)-2-me thylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and therefore prevent the curved-to-straight structural transition of tubulin, which is required for microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. In addition, TUB091 displayed vascular disrupting effects in vitro and in the chicken chorioallantoic membrane (CAM) assay at low nanomolar concentrations. A water-soluble L-Lys-L-Pro derivative of TUB091 (i.e. TUB099) showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic activity similar to that of combretastatin A4-phosphate. Our data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, we provide evidence that our prodrug approach may be valuable for the development of anti-cancer drugs.

Antivascular and antitumor properties of the tubulin-binding chalcone TUB091.,Canela MD, Noppen S, Bueno O, Prota AE, Bargsten K, Saez-Calvo G, Jimeno ML, Benkheil M, Ribatti D, Velazquez S, Camarasa MJ, Diaz JF, Steinmetz MO, Priego EM, Perez-Perez MJ, Liekens S Oncotarget. 2016 May 20. doi: 10.18632/oncotarget.9527. PMID:27224920^[4]

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

References

↑ Nakao C, Itoh TJ, Hotani H, Mori N. Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. J Biol Chem. 2004 May 28;279(22):23014-21. Epub 2004 Mar 22. PMID:15039434 doi:http://dx.doi.org/10.1074/jbc.M313693200
↑ Gavet O, El Messari S, Ozon S, Sobel A. Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons. J Neurosci Res. 2002 Jun 1;68(5):535-50. PMID:12111843 doi:http://dx.doi.org/10.1002/jnr.10234
↑ Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504 doi:http://dx.doi.org/10.1038/nature02393
↑ Canela MD, Noppen S, Bueno O, Prota AE, Bargsten K, Saez-Calvo G, Jimeno ML, Benkheil M, Ribatti D, Velazquez S, Camarasa MJ, Diaz JF, Steinmetz MO, Priego EM, Perez-Perez MJ, Liekens S. Antivascular and antitumor properties of the tubulin-binding chalcone TUB091. Oncotarget. 2016 May 20. doi: 10.18632/oncotarget.9527. PMID:27224920 doi:http://dx.doi.org/10.18632/oncotarget.9527

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jvd"

@@ Line 1: / Line 1: @@
 ==Tubulin-TUB092 complex==
-<StructureSection load='5jvd' size='340' side='right' caption='[[5jvd]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
+<StructureSection load='5jvd' size='340' side='right'caption='[[5jvd]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jvd]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JVD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JVD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jvd]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JVD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JVD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NL:(2E)-3-(3-HYDROXY-4-METHOXYPHENYL)-1-(7-METHOXY-2H-1,3-BENZODIOXOL-5-YL)-2-METHYLPROP-2-EN-1-ONE'>6NL</scene>, <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NL:(2E)-3-(3-HYDROXY-4-METHOXYPHENYL)-1-(7-METHOXY-2H-1,3-BENZODIOXOL-5-YL)-2-METHYLPROP-2-EN-1-ONE'>6NL</scene>, <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jvd OCA], [http://pdbe.org/5jvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jvd RCSB], [http://www.ebi.ac.uk/pdbsum/5jvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jvd ProSAT]</span></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=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://proteopedia.org/fgij/fg.htm?mol=5jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jvd OCA], [http://pdbe.org/5jvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jvd RCSB], [http://www.ebi.ac.uk/pdbsum/5jvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jvd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
 ==See Also==
-*[[Stathmin|Stathmin]]
+*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
+*[[Tubulin 3D Structures|Tubulin 3D Structures]]
+*[[User:Alisa Cario|User:Alisa Cario]]
 == References ==
 <references/>
@@ Line 26: / Line 29: @@
 </StructureSection>
 [[Category: Bos taurus]]
+[[Category: Buffalo rat]]
+[[Category: Chick]]
+[[Category: Large Structures]]
 [[Category: Bargsten, K]]
 [[Category: Benkheil, M]]

5jvd

From Proteopedia

Revision as of 11:41, 17 June 2020

Tubulin-TUB092 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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