OCA at 16:11, 29 November 2023

OCA — Wed, 29 Nov 2023 16:11:22 GMT

←Older revision		Revision as of 16:11, 29 November 2023
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-	====	+	==NCI-1 in complex with CRM1-Ran-RanBP1==
-	<StructureSection load='7cnd' size='340' side='right'caption='[[7cnd]]' scene=''>	+	<StructureSection load='7cnd' size='340' side='right'caption='[[7cnd]], [[Resolution\|resolution]] 1.80Å' 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'>[[7cnd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CND OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CND 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=7cnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cnd OCA], [https://pdbe.org/7cnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cnd RCSB], [https://www.ebi.ac.uk/pdbsum/7cnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cnd 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]] 1.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=G6U:~{N}-[(~{E})-3-[3,5-bis(trifluoromethyl)phenyl]sulfinylprop-2-enyl]-3-methyl-butan-1-amine'>G6U</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</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=7cnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cnd OCA], [https://pdbe.org/7cnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cnd RCSB], [https://www.ebi.ac.uk/pdbsum/7cnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cnd ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RAN_HUMAN RAN_HUMAN] GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref> Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nuclear export factor chromosome region maintenance 1 (CRM1) is an attractive anticancer and antiviral drug target that spurred several research efforts to develop its inhibitor. Noncovalent CRM1 inhibitors are desirable, but none is reported to date. Here, we present the crystal structure of yeast CRM1 in complex with S109, a substructure of CBS9106 (under clinical test). Superimposition with the LFS-829 (another covalent CRM1 inhibitor) complex inspired the design of a noncovalent CRM1 inhibitor. Among nine synthesized compounds, noncovalent CRM1 inhibitor 1 (NCI-1) showed a high affinity to human and yeast CRM1 in the absence or presence of GST-bound Ras-related nuclear protein (RanGTP). Unlike covalent inhibitors, the crystal structure showed that NCI-1 is bound in the "open" nuclear export signal (NES) groove of CRM1, simultaneously occupying two hydrophobic pockets. NCI-1 additionally inhibited the nuclear export and proliferation of cells harboring the human CRM1-C528S mutant. Our work opens up the avenue of noncovalent CRM1 inhibitor development toward a more potent, less toxic, and broad-spectrum anticancer/antiviral therapy.
		+
		+	Structure-Guided Design of the First Noncovalent Small-Molecule Inhibitor of CRM1.,Lei Y, An Q, Shen XF, Sui M, Li C, Jia D, Luo Y, Sun Q J Med Chem. 2021 May 27;64(10):6596-6607. doi: 10.1021/acs.jmedchem.0c01675. Epub , 2021 May 11. PMID:33974430<ref>PMID:33974430</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7cnd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Saccharomyces cerevisiae]]
		+	[[Category: Lei Y]]
		+	[[Category: Sun Q]]

OCA at 12:12, 9 June 2021

OCA — Wed, 09 Jun 2021 12:12:37 GMT

←Older revision		Revision as of 12:12, 9 June 2021
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-	'''Unreleased structure'''

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

OCA at 04:07, 14 October 2020

OCA — Wed, 14 Oct 2020 04:07:30 GMT

←Older revision		Revision as of 04:07, 14 October 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 05 Aug 2020 04:12:29 GMT

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

←Older revision

Revision as of 04:12, 5 August 2020

OCA: New page: '''Unreleased structure''' The entry 7cnd is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 05 Aug 2020 04:12:27 GMT

New page: '''Unreleased structure''' The entry 7cnd is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7cnd is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7cnd - Revision history

OCA at 16:11, 29 November 2023

OCA at 12:12, 9 June 2021

OCA at 04:07, 14 October 2020

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

OCA: New page: '''Unreleased structure''' The entry 7cnd is ON HOLD Authors: Description: Category: Unreleased Structures