OCA at 16:46, 29 November 2023

OCA — Wed, 29 Nov 2023 16:46:21 GMT

←Older revision		Revision as of 16:46, 29 November 2023
Line 1:		Line 1:

-	====	+	==Crystal structure of tubulin in complex with L-DM1-SMe==
-	<StructureSection load='7e4q' size='340' side='right'caption='[[7e4q]]' scene=''>	+	<StructureSection load='7e4q' size='340' side='right'caption='[[7e4q]], [[Resolution\|resolution]] 2.50Å' 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'>[[7e4q]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E4Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E4Q 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=7e4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e4q OCA], [https://pdbe.org/7e4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e4q RCSB], [https://www.ebi.ac.uk/pdbsum/7e4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e4q 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]] 2.501Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=BKX:(1S,2R,3R,5R,6R,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1~10,14~.0~3,5~]hexacosa-10(26),11,13,16,18-pentaen-6-yl+(2S)-2-{methyl[3-(methyldisulfanyl)propanoyl]amino}propanoate+(non-preferred+name)'>BKX</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=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=7e4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e4q OCA], [https://pdbe.org/7e4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e4q RCSB], [https://www.ebi.ac.uk/pdbsum/7e4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e4q ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://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).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Maytansinoids, the chemical derivatives of Maytansine, are commonly used as potent cytotoxic payloads in antibody-drug conjugates (ADC). Structure-activity-relationship studies had identified the C3 ester side chain as a critical element for antitumor activity of maytansinoids. The maytansinoids bearing the methyl group at C3 position with D configuration were about 100 to 400-fold less cytotoxic than their corresponding L-epimers toward various cell lines. The detailed mechanism of how chirality affects the anticancer activity remains elusive. In this study, we determined the high-resolution crystal structure of tubulin in complex with maytansinol, L-DM1-SMe and D-DM1-SMe. And we found the carbonyl oxygen atom of the ester moiety and the tail thiomethyl group at C3 side chain of L-DM1-SMe form strong intramolecular interaction with the hydroxyl at position 9 and the benzene ring, respectively, fixing the bioactive conformation and enhancing the binding affinity. Additionally, ligand-based and structure-based virtually screening methods were used to screen the commercially macrocyclic compounds library, and 15 macrocyclic structures were picketed out as putatively new maytansine-site inhibitors. Our study provides a possible strategy for the rational discovery of next-generation maytansine site inhibitors.
		+
		+	C3 ester side chain plays a pivotal role in the antitumor activity of Maytansinoids.,Li W, Huang M, Li Y, Xia A, Tan L, Zhang Z, Wang Y, Yang J Biochem Biophys Res Commun. 2021 Aug 20;566:197-203. doi: , 10.1016/j.bbrc.2021.05.071. Epub 2021 Jun 15. PMID:34144258<ref>PMID:34144258</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7e4q" 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: Bos taurus]]
		+	[[Category: Gallus gallus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Rattus norvegicus]]
		+	[[Category: Li W]]
		+	[[Category: Wang Y]]

OCA at 09:56, 7 July 2021

OCA — Wed, 07 Jul 2021 09:56:37 GMT

←Older revision		Revision as of 09:56, 7 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7e4q ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7e4q' size='340' side='right'caption='[[7e4q]]' scene=''>
-	~~Authors~~: ~~Wang, Y~~.~~, Li, W~~.	+	== 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 tubulin in complex with L~~-~~DM1-SMe~~	+	</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=7e4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e4q OCA], [https://pdbe.org/7e4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e4q RCSB], [https://www.ebi.ac.uk/pdbsum/7e4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e4q ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Wang, Y~~]]	+	__TOC__
-	[[Category: ~~Li, W~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 09:14, 31 March 2021

OCA — Wed, 31 Mar 2021 09:14:02 GMT

←Older revision		Revision as of 09:14, 31 March 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7e4q is ON HOLD	+	The entry 7e4q is ON HOLD until Paper Publication

	Authors: Wang, Y., Li, W.		Authors: Wang, Y., Li, W.

OCA: Protected "7e4q" [edit=sysop:move=sysop]

OCA — Wed, 24 Feb 2021 05:34:09 GMT

Protected "7e4q" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:34, 24 February 2021

OCA: New page: '''Unreleased structure''' The entry 7e4q is ON HOLD Authors: Wang, Y., Li, W. Description: Crystal structure of tubulin in complex with L-DM1-SMe Category: Unreleased Structures [...

OCA — Wed, 24 Feb 2021 05:34:08 GMT

New page: '''Unreleased structure''' The entry 7e4q is ON HOLD Authors: Wang, Y., Li, W. Description: Crystal structure of tubulin in complex with L-DM1-SMe Category: Unreleased Structures [...

New page

'''Unreleased structure'''

The entry 7e4q is ON HOLD

Authors: Wang, Y., Li, W.

Description: Crystal structure of tubulin in complex with L-DM1-SMe
[[Category: Unreleased Structures]]
[[Category: Wang, Y]]
[[Category: Li, W]]

7e4q - Revision history

OCA at 16:46, 29 November 2023

OCA at 09:56, 7 July 2021

OCA at 09:14, 31 March 2021

OCA: Protected "7e4q" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7e4q is ON HOLD Authors: Wang, Y., Li, W. Description: Crystal structure of tubulin in complex with L-DM1-SMe Category: Unreleased Structures [...