7dp8 - Revision history

OCA at 16:37, 29 November 2023

OCA — Wed, 29 Nov 2023 16:37:30 GMT

←Older revision		Revision as of 16:37, 29 November 2023
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-	====	+	==Crystal structure of T2R-TTL-Cevipabulin-eribulin complex==
-	<StructureSection load='7dp8' size='340' side='right'caption='[[7dp8]]' scene=''>	+	<StructureSection load='7dp8' size='340' side='right'caption='[[7dp8]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7dp8]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DP8 FirstGlance]. <br>
-	</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=7dp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dp8 OCA], [https://pdbe.org/7dp8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dp8 RCSB], [https://www.ebi.ac.uk/pdbsum/7dp8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dp8 ProSAT]</span></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]] 2.446Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6K9:(1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-AMINO-2-HYDROXYPROPYL]-21-METHOXY-14-METHYL-8,15-DIMETHYLIDENE-2,19,30,34,37,39,40,41-OCTAOXANONACYCLO[24.9.2.1~3,32~.1~3,33~.1~6,9~.1~12,16~.0~18,22~.0~29,36~.0~31,35~]HENTETRACONTAN-24-ONE+(NON-PREFERRED+NAME)'>6K9</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=G2X:6-[2,6-bis(fluoranyl)-4-[3-(methylamino)propoxy]phenyl]-5-chloranyl-N-[(2S)-1,1,1-tris(fluoranyl)propan-2-yl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine'>G2X</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'>[https://proteopedia.org/fgij/fg.htm?mol=7dp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dp8 OCA], [https://pdbe.org/7dp8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dp8 RCSB], [https://www.ebi.ac.uk/pdbsum/7dp8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dp8 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Microtubules, composed of alphabeta-tubulin heterodimers, have remained popular anticancer targets for decades. Six known binding sites on tubulin dimers have been identified thus far, with five sites on beta-tubulin and only one site on alpha-tubulin, hinting that compounds binding to alpha-tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our x-ray crystallography study reveals that, in addition to binding to the vinblastine site, cevipabulin also binds to a new site on alpha-tubulin. We find that cevipabulin at this site pushes the alphaT5 loop outward, making the nonexchangeable GTP exchangeable, which reduces the stability of tubulin, leading to its destabilization and degradation. Our results confirm the existence of a new agent binding site on alpha-tubulin and shed light on the development of tubulin degraders as a new generation of antimicrotubule drugs targeting this novel site.
		+
		+	Cevipabulin-tubulin complex reveals a novel agent binding site on alpha-tubulin with tubulin degradation effect.,Yang J, Yu Y, Li Y, Yan W, Ye H, Niu L, Tang M, Wang Z, Yang Z, Pei H, Wei H, Zhao M, Wen J, Yang L, Ouyang L, Wei Y, Chen Q, Li W, Chen L Sci Adv. 2021 May 19;7(21):eabg4168. doi: 10.1126/sciadv.abg4168. Print 2021 May. PMID:34138737<ref>PMID:34138737</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7dp8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Stathmin-4 3D structures\|Stathmin-4 3D structures]]
		+	*[[Tubulin 3D Structures\|Tubulin 3D Structures]]
		+	*[[Tubulin tyrosine ligase\|Tubulin tyrosine ligase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Gallus gallus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Rattus norvegicus]]
		+	[[Category: Sus scrofa]]
		+	[[Category: Chen LJ]]
		+	[[Category: Chen Q]]
		+	[[Category: Yang JH]]
		+	[[Category: Yu Y]]

OCA at 09:56, 7 July 2021

OCA — Wed, 07 Jul 2021 09:56:27 GMT

←Older revision		Revision as of 09:56, 7 July 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7dp8 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7dp8' size='340' side='right'caption='[[7dp8]]' scene=''>
-	~~Authors~~: ~~Chen, L~~.J.~~, Chen, Q~~.~~, Yu, Y~~.~~, Yang, J~~.H.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of T2R-TTL-Cevipabulin-eribulin complex~~	+	</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=7dp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dp8 OCA], [https://pdbe.org/7dp8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dp8 RCSB], [https://www.ebi.ac.uk/pdbsum/7dp8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dp8 ProSAT]</span></td></tr>
-	[~~[Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Yu, Y~~]]	+	__TOC__
-	[~~[Category~~: ~~Chen, Q~~]]	+	</StructureSection>
-	[[Category: ~~Chen, L.J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Yang, J.H~~]]	+	[[Category: Z-disk]]

OCA at 05:21, 30 December 2020

OCA — Wed, 30 Dec 2020 05:21:47 GMT

←Older revision		Revision as of 05:21, 30 December 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7dp8 is ON HOLD	+	The entry 7dp8 is ON HOLD until Paper Publication

	Authors: Chen, L.J., Chen, Q., Yu, Y., Yang, J.H.		Authors: Chen, L.J., Chen, Q., Yu, Y., Yang, J.H.
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Yu, Y]]		[[Category: Yu, Y]]
-	[[Category: Yang, J.H]]
-	[[Category: Chen, L.J]]
	[[Category: Chen, Q]]		[[Category: Chen, Q]]
		+	[[Category: Chen, L.J]]
		+	[[Category: Yang, J.H]]

OCA: Protected "7dp8" [edit=sysop:move=sysop]

OCA — Thu, 24 Dec 2020 07:58:04 GMT

Protected "7dp8" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:58, 24 December 2020

OCA: New page: '''Unreleased structure''' The entry 7dp8 is ON HOLD Authors: Chen, L.J., Chen, Q., Yu, Y., Yang, J.H. Description: Crystal structure of T2R-TTL-Cevipabulin-eribulin complex [[Category...

OCA — Thu, 24 Dec 2020 07:58:02 GMT

New page: '''Unreleased structure''' The entry 7dp8 is ON HOLD Authors: Chen, L.J., Chen, Q., Yu, Y., Yang, J.H. Description: Crystal structure of T2R-TTL-Cevipabulin-eribulin complex [[Category...

New page

'''Unreleased structure'''

The entry 7dp8 is ON HOLD

Authors: Chen, L.J., Chen, Q., Yu, Y., Yang, J.H.

Description: Crystal structure of T2R-TTL-Cevipabulin-eribulin complex
[[Category: Unreleased Structures]]
[[Category: Yu, Y]]
[[Category: Yang, J.H]]
[[Category: Chen, L.J]]
[[Category: Chen, Q]]