6g6z - Revision history

OCA at 09:45, 18 November 2020

OCA — Wed, 18 Nov 2020 09:45:32 GMT

←Older revision		Revision as of 09:45, 18 November 2020
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	==Eg5-inhibitor complex==		==Eg5-inhibitor complex==
-	<StructureSection load='6g6z' size='340' side='right' caption='[[6g6z]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='6g6z' size='340' side='right'caption='[[6g6z]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6g6z]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G6Z OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6G6Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6g6z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G6Z OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6G6Z FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EOK:(~{N}~{Z})-~{N}-[(5~{S})-4-ethanoyl-5-methyl-5-phenyl-1,3,4-thiadiazolidin-2-ylidene]ethanamide'>EOK</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=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EOK:(~{N}~{Z})-~{N}-[(5~{S})-4-ethanoyl-5-methyl-5-phenyl-1,3,4-thiadiazolidin-2-ylidene]ethanamide'>EOK</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=6g6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g6z OCA], [http://pdbe.org/6g6z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g6z RCSB], [http://www.ebi.ac.uk/pdbsum/6g6z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g6z ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KIF11, EG5, KNSL1, TRIP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6g6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g6z OCA], [http://pdbe.org/6g6z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g6z RCSB], [http://www.ebi.ac.uk/pdbsum/6g6z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g6z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Kozielski, F]]		[[Category: Kozielski, F]]
	[[Category: Talapatra, S K]]		[[Category: Talapatra, S K]]

OCA at 21:55, 9 August 2018

OCA — Thu, 09 Aug 2018 21:55:03 GMT

←Older revision		Revision as of 21:55, 9 August 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6g6z is ~~ON HOLD~~ ~~until Apr 04 2020~~	+	==Eg5-inhibitor complex==
		+	<StructureSection load='6g6z' size='340' side='right' caption='[[6g6z]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6g6z]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G6Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G6Z FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EOK:(~{N}~{Z})-~{N}-[(5~{S})-4-ethanoyl-5-methyl-5-phenyl-1,3,4-thiadiazolidin-2-ylidene]ethanamide'>EOK</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=6g6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g6z OCA], [http://pdbe.org/6g6z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g6z RCSB], [http://www.ebi.ac.uk/pdbsum/6g6z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g6z ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[http://omim.org/entry/152950 152950]]. An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.<ref>PMID:22284827</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The thiadiazole scaffold is an important core moiety in a variety of clinical drug candidates targeting a range of diseases. For example, the 2,4,5-substituted 1,3,4-thiadiazole scaffold is present in a lead compound and at least two clinical candidates targeting the human motor protein Eg5, against neoplastic diseases. An inhibitor named K858 has in vivo activity in various mouse xenografts whereas the clinical candidates (S)-ARRY-520 and (R)-Litronesib have entered clinical trials with the former one in phase III clinical trials either alone or in combination with a proteasome inhibitor against relapsed/refractory multiple myeloma. Astonishingly, structural data are lacking for all thiadiazole-containing Eg5 inhibitors. Here we report the structure determination of two crystal forms of the ternary Eg5-ADP-K858 complex, locking the motor in the so-called final inhibitor bound state, thus blocking ADP release, a crucial stage for Eg5 activity. K858 acts at the established allosteric inhibitor-binding pocket formed of helix alpha2, loop L5 and helix alpha3. The structure of the complex has far reaching consequences for thiadiazole containing Eg5 inhibitors. For example, we could rationalise the structure-activity relationship in the crucial 5-position of the thiadiazole scaffold and the complex will serve in the future as a basis for strucutre-based drug design.

-	~~Authors~~:	+	Crystal structure of the Eg5 - K858 complex and implications for structure-based design of thiadiazole-containing inhibitors.,Talapatra SK, Tham CL, Guglielmi P, Cirilli R, Chandrasekaran B, Karpoormath R, Carradori S, Kozielski F Eur J Med Chem. 2018 Jul 4;156:641-651. doi: 10.1016/j.ejmech.2018.07.006. PMID:30031975<ref>PMID:30031975</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6g6z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Kozielski, F]]
		+	[[Category: Talapatra, S K]]
		+	[[Category: Tham, C L]]
		+	[[Category: Cell cycle]]
		+	[[Category: Eg5]]
		+	[[Category: Eg5-inhibitor]]
		+	[[Category: Kif11]]

OCA at 04:25, 18 April 2018

OCA — Wed, 18 Apr 2018 04:25:22 GMT

←Older revision		Revision as of 04:25, 18 April 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6g6z is ON HOLD	+	The entry 6g6z is ON HOLD until Apr 04 2020

	Authors:		Authors:

OCA: Protected "6g6z" [edit=sysop:move=sysop]

OCA — Wed, 11 Apr 2018 12:41:21 GMT

Protected "6g6z" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:41, 11 April 2018

OCA: New page: '''Unreleased structure''' The entry 6g6z is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 11 Apr 2018 12:41:19 GMT

New page: '''Unreleased structure''' The entry 6g6z is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6g6z is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]