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==Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(K541Q,K542Q,R543S,K545Q,K548Q,K579Q)-Ran-RanBP1==
==Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(K541Q,K542Q,R543S,K545Q,K548Q,K579Q)-Ran-RanBP1==
<StructureSection load='4hb0' size='340' side='right' caption='[[4hb0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='4hb0' size='340' side='right'caption='[[4hb0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4hb0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HB0 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4hb0]] 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=4HB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HB0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=LBF:LEPTOMYCIN+B'>LBF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.2&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gmx|4gmx]], [[4gpt|4gpt]], [[4hat|4hat]], [[4hau|4hau]], [[4hav|4hav]], [[4haw|4haw]], [[4hax|4hax]], [[4hay|4hay]], [[4haz|4haz]], [[4hb2|4hb2]], [[4hb3|4hb3]], [[4hb4|4hb4]]</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=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=LBF:LEPTOMYCIN+B'>LBF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAN, ARA24, OK/SW-cl.81 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), YRB1, CST20, HTN1, SFO1, YDR002W, YD8119.08 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), CRM1, KAP124, XPO1, YGR218W, G8514 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=4hb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hb0 OCA], [https://pdbe.org/4hb0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hb0 RCSB], [https://www.ebi.ac.uk/pdbsum/4hb0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hb0 ProSAT]</span></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=4hb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hb0 OCA], [http://pdbe.org/4hb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hb0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hb0 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>  [[http://www.uniprot.org/uniprot/XPO1_YEAST XPO1_YEAST]] Receptor for the leucine-rich nuclear export signal (NES). [[http://www.uniprot.org/uniprot/YRB1_YEAST YRB1_YEAST]] Important for the export of protein containing nuclear export signal (NES) out of the nucleus. Stimulates the GTPase activity of GSP1 and GSP2.  
[https://www.uniprot.org/uniprot/YRB1_YEAST YRB1_YEAST] Important for the export of protein containing nuclear export signal (NES) out of the nucleus. Stimulates the GTPase activity of GSP1 and GSP2.
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</div>
</div>
<div class="pdbe-citations 4hb0" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 4hb0" style="background-color:#fffaf0;"></div>
==See Also==
*[[Exportin 3D structures|Exportin 3D structures]]
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Atcc 18824]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Chook, Y M]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Sun, Q]]
[[Category: Chook YM]]
[[Category: Heat repeat]]
[[Category: Sun Q]]
[[Category: Leptomycin b]]
[[Category: Lmb]]
[[Category: Nuclear export]]
[[Category: Protein transport-antibiotic complex]]
[[Category: Ran-ranbp1]]

Latest revision as of 10:01, 27 November 2024

Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(K541Q,K542Q,R543S,K545Q,K548Q,K579Q)-Ran-RanBP1Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(K541Q,K542Q,R543S,K545Q,K548Q,K579Q)-Ran-RanBP1

Structural highlights

4hb0 is a 3 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

YRB1_YEAST Important for the export of protein containing nuclear export signal (NES) out of the nucleus. Stimulates the GTPase activity of GSP1 and GSP2.

Publication Abstract from PubMed

The polyketide natural product Leptomycin B inhibits nuclear export mediated by the karyopherin protein chromosomal region maintenance 1 (CRM1). Here, we present 1.8- to 2.0-A-resolution crystal structures of CRM1 bound to Leptomycin B and related inhibitors Anguinomycin A and Ratjadone A. Structural and complementary chemical analyses reveal an unexpected mechanism of inhibition involving covalent conjugation and CRM1-mediated hydrolysis of the natural products' lactone rings. Furthermore, mutagenesis reveals the mechanism of hydrolysis by CRM1. The nuclear export signal (NES)-binding groove of CRM1 is able to drive a chemical reaction in addition to binding protein cargos for transport through the nuclear pore complex.

Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1.,Sun Q, Carrasco YP, Hu Y, Guo X, Mirzaei H, Macmillan J, Chook YM Proc Natl Acad Sci U S A. 2013 Jan 7. PMID:23297231[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Sun Q, Carrasco YP, Hu Y, Guo X, Mirzaei H, Macmillan J, Chook YM. Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1. Proc Natl Acad Sci U S A. 2013 Jan 7. PMID:23297231 doi:http://dx.doi.org/10.1073/pnas.1217203110

4hb0, resolution 2.20Å

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