OCA at 07:05, 25 October 2023

OCA — Wed, 25 Oct 2023 07:05:36 GMT

←Older revision		Revision as of 07:05, 25 October 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8hq3 is ~~ON HOLD until Paper~~ Publication	+	==KL1 in complex with CRM1-Ran-RanBP1==
		+	<StructureSection load='8hq3' size='340' side='right'caption='[[8hq3]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8hq3]] 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=8HQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HQ3 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.1Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MI8:methyl+(3~{S},5~{R},6~{E},8~{Z},10~{R},12~{E},14~{E},16~{R})-3,16-bis(azanyl)-8,10,12-trimethyl-16-[(2~{S},4~{R},5~{S},6~{S})-5-methyl-4-oxidanyl-6-[(~{E})-prop-1-enyl]oxan-2-yl]-5-oxidanyl-hexadeca-6,8,12,14-tetraenoate'>MI8</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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=8hq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hq3 OCA], [https://pdbe.org/8hq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hq3 RCSB], [https://www.ebi.ac.uk/pdbsum/8hq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hq3 ProSAT]</span></td></tr>
		+	</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 ==
		+	Cancer cells frequently utilize elevated nuclear export to escape tumor suppression and gain proliferative advantage. Chromosome Region Maintenance 1 (CRM1/XPO1) mediates macromolecule nuclear export and plays an important role in tumorigenesis and progression. The clinical approval of its covalent inhibitor KPT-330 (Selinexor) validates the feasibility of targeting CRM1 to treat cancers. Here, we synthesized four aminoratjadone derivatives and found that two of them, KL1 and KL2, are noncovalent CRM1 inhibitors. The two compounds underwent spontaneous hydrolysis in aqueous buffers, and the resulting products were more active against CRM1. High-resolution crystal structures revealed the CRM1-binding mode of these compounds and explained the observed structure-activity relationships. In cells, KL1 and KL2 localized CRM1 in the nuclear periphery and led to depletion of nuclear CRM1, thereby inhibiting the nuclear export and growth of colorectal cancer cells at submicromolar concentrations. This work lays the foundation for further development of aminoratjadone-based noncovalent CRM1 inhibitors.

-	~~Authors: Sun, Q~~., Jian, L.	+	Discovery of Aminoratjadone Derivatives as Potent Noncovalent CRM1 Inhibitors.,Jian L, Zscherp R, Beutling U, Shen X, Xu S, Zhang X, Bronstrup M, Klahn P, Sun Q J Med Chem. 2023 Sep 14;66(17):11940-11950. doi: 10.1021/acs.jmedchem.3c00549. , Epub 2023 Aug 18. PMID:37595020<ref>PMID:37595020</ref>

-	~~Description: KL1 in complex with CRM1~~-~~Ran~~-~~RanBP1~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Sun, Q~~]]	+	<div class="pdbe-citations 8hq3" style="background-color:#fffaf0;"></div>
-	[[Category: Jian, L]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Saccharomyces cerevisiae]]
		+	[[Category: Jian L]]
		+	[[Category: Sun Q]]

OCA at 05:04, 25 January 2023

OCA — Wed, 25 Jan 2023 05:04:39 GMT

←Older revision		Revision as of 05:04, 25 January 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8hq3 is ON HOLD	+	The entry 8hq3 is ON HOLD until Paper Publication

	Authors: Sun, Q., Jian, L.		Authors: Sun, Q., Jian, L.

-	Description: ~~KL2~~ in complex with CRM1-Ran-RanBP1	+	Description: KL1 in complex with CRM1-Ran-RanBP1
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Sun, Q]]		[[Category: Sun, Q]]
	[[Category: Jian, L]]		[[Category: Jian, L]]

OCA: Protected "8hq3" [edit=sysop:move=sysop]

OCA — Wed, 21 Dec 2022 07:12:12 GMT

Protected "8hq3" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:12, 21 December 2022

OCA: New page: '''Unreleased structure''' The entry 8hq3 is ON HOLD Authors: Sun, Q., Jian, L. Description: KL2 in complex with CRM1-Ran-RanBP1 Category: Unreleased Structures [[Category: Sun, Q]...

OCA — Wed, 21 Dec 2022 07:12:11 GMT

New page: '''Unreleased structure''' The entry 8hq3 is ON HOLD Authors: Sun, Q., Jian, L. Description: KL2 in complex with CRM1-Ran-RanBP1 Category: Unreleased Structures [[Category: Sun, Q]...

New page

'''Unreleased structure'''

The entry 8hq3 is ON HOLD

Authors: Sun, Q., Jian, L.

Description: KL2 in complex with CRM1-Ran-RanBP1
[[Category: Unreleased Structures]]
[[Category: Sun, Q]]
[[Category: Jian, L]]

8hq3 - Revision history

OCA at 07:05, 25 October 2023

OCA at 05:04, 25 January 2023

OCA: Protected "8hq3" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8hq3 is ON HOLD Authors: Sun, Q., Jian, L. Description: KL2 in complex with CRM1-Ran-RanBP1 Category: Unreleased Structures [[Category: Sun, Q]...