4haz

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[[Image:4haz.png|left|200px]]
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==Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(R543S,K548E,K579Q)-Ran-RanBP1==
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<StructureSection load='4haz' size='340' side='right' caption='[[4haz]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4haz]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HAZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HAZ FirstGlance]. <br>
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</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>
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<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]], [[4hb0|4hb0]], [[4hb2|4hb2]], [[4hb3|4hb3]], [[4hb4|4hb4]]</td></tr>
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<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 Homo sapiens]), YRB1, CST20, HTN1, SFO1, YDR002W, YD8119.08 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), CRM1, KAP124, XPO1, YGR218W, G8514 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>
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<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=4haz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4haz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4haz RCSB], [http://www.ebi.ac.uk/pdbsum/4haz PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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{{STRUCTURE_4haz| PDB=4haz | SCENE= }}
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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<ref>PMID:23297231</ref>
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===Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(R543S,K548E,K579Q)-Ran-RanBP1===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_23297231}}
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==See Also==
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*[[Exportin|Exportin]]
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==About this Structure==
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*[[GTP-binding protein|GTP-binding protein]]
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[[4haz]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HAZ OCA].
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
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[[Category: Chook, Y M.]]
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[[Category: Chook, Y M]]
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[[Category: Sun, Q.]]
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[[Category: Sun, Q]]
[[Category: Heat repeat]]
[[Category: Heat repeat]]
[[Category: Leptomycin b]]
[[Category: Leptomycin b]]

Revision as of 09:40, 10 December 2014

Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(R543S,K548E,K579Q)-Ran-RanBP1

4haz, resolution 1.90Å

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