1q0b

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{{STRUCTURE_1q0b| PDB=1q0b | SCENE= }}
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==Crystal structure of the motor protein KSP in complex with ADP and monastrol==
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===Crystal structure of the motor protein KSP in complex with ADP and monastrol===
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<StructureSection load='1q0b' size='340' side='right' caption='[[1q0b]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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{{ABSTRACT_PUBMED_14672662}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1q0b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q0B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Q0B FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAT:ETHYL+4-(3-HYDROXYPHENYL)-6-METHYL-2-THIOXO-1,2,3,4-TETRAHYDROPYRIMIDINE-5-CARBOXYLATE'>NAT</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIF11 OR KNSL1 OR EG5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q0b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1q0b RCSB], [http://www.ebi.ac.uk/pdbsum/1q0b PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[http://omim.org/entry/152950 152950]]. An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.<ref>PMID:22284827</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q0/1q0b_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9 A resolution structure of the motor domain of KSP, bound with the small molecule monastrol and Mg2+ x ADP, reveals that monastrol confers inhibition by "induced-fitting" onto the protein some 12 A away from the catalytic center of the enzyme, resulting in the creation of a previously non-existing binding pocket. The structure provides new insights into the biochemical and mechanical mechanisms of the mitotic motor domain. Inhibition of KSP provides a novel mechanism to arrest mitotic spindle formation, a target of several approved and investigative anti-cancer agents. The structural information gleaned from this novel pocket offers a new angle for the design of anti-mitotic agents.
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==Disease==
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Inhibition of a mitotic motor protein: where, how, and conformational consequences.,Yan Y, Sardana V, Xu B, Homnick C, Halczenko W, Buser CA, Schaber M, Hartman GD, Huber HE, Kuo LC J Mol Biol. 2004 Jan 9;335(2):547-54. PMID:14672662<ref>PMID:14672662</ref>
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[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[http://omim.org/entry/152950 152950]]. An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.<ref>PMID:22284827</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>
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</div>
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==About this Structure==
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[[1q0b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q0B OCA].
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==See Also==
==See Also==
*[[Kinesin|Kinesin]]
*[[Kinesin|Kinesin]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:014672662</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Buser, C A.]]
[[Category: Buser, C A.]]

Revision as of 16:03, 29 September 2014

Crystal structure of the motor protein KSP in complex with ADP and monastrol

1q0b, resolution 1.90Å

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