View source for 6m6x


==Oridonin in complex with CRM1#-Ran-RanBP1==
<StructureSection load='6m6x' size='340' side='right'caption='[[6m6x]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6m6x]] 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_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M6X 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]] 2.88&#8491;</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ODN:(1BETA,6BETA,7BETA,8ALPHA,9BETA,10ALPHA,13ALPHA,14R,16BETA)-1,6,7,14-TETRAHYDROXY-7,20-EPOXYKAURAN-15-ONE'>ODN</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=6m6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m6x OCA], [https://pdbe.org/6m6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m6x RCSB], [https://www.ebi.ac.uk/pdbsum/6m6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m6x 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 ==
The protein chromosome region maintenance 1 (CRM1) is an important nuclear export factor and drug target in diseases such as cancer and viral infections. Several plant-derived CRM1 inhibitors including plumbagin and oridonin possess potent antitumor activities. However, their modes of CRM1 inhibition remain unclear. Here, a multimutant CRM1 was engineered to enable crystallization of these two small molecules in its NES groove. Plumbagin and oridonin share the same three conjugation sites in CRM1. In solution, these two inhibitors targeted more CRM1 sites and inhibited its activity through promoting its aggregation, in addition to directly targeting the NES groove. While the plumbagin-bound NES groove resembles the NES-bound groove state, the oridonin complex reveals for the first time a more open NES groove. The observed greater NES groove dynamics may improve cargo loading through a "capture-and-tighten" mechanism. This work thus provides new insights on the mechanism of CRM1 inhibition by two natural products and a structural basis for further development of these or other CRM1 inhibitors.

Novel Mechanistic Observations and NES-Binding Groove Features Revealed by the CRM1 Inhibitors Plumbagin and Oridonin.,Lei Y, Li Y, Tan Y, Qian Z, Zhou Q, Jia D, Sun Q J Nat Prod. 2021 May 28;84(5):1478-1488. doi: 10.1021/acs.jnatprod.0c01231. Epub , 2021 Apr 23. PMID:33890470<ref>PMID:33890470</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6m6x" style="background-color:#fffaf0;"></div>

==See Also==
*[[Exportin 3D structures|Exportin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Lei Y]]
[[Category: Sun Q]]