3k3b
From Proteopedia
(Difference between revisions)
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==Co-crystal structure of the human kinesin Eg5 with a novel tetrahydro-beta-carboline== | ==Co-crystal structure of the human kinesin Eg5 with a novel tetrahydro-beta-carboline== | ||
| - | <StructureSection load='3k3b' size='340' side='right' caption='[[3k3b]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='3k3b' size='340' side='right'caption='[[3k3b]], [[Resolution|resolution]] 2.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3k3b]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3k3b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K3B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=L31:3-[(1R)-2-ACETYL-6-METHYL-2,3,4,9-TETRAHYDRO-1H-BETA-CARBOLIN-1-YL]PHENOL'>L31</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=L31:3-[(1R)-2-ACETYL-6-METHYL-2,3,4,9-TETRAHYDRO-1H-BETA-CARBOLIN-1-YL]PHENOL'>L31</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3k3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k3b OCA], [https://pdbe.org/3k3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k3b RCSB], [https://www.ebi.ac.uk/pdbsum/3k3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k3b ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://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:[https://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> |
== Function == | == Function == | ||
| - | [ | + | [https://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> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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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/main_output.php?pdb_ID=3k3b ConSurf]. | </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/main_output.php?pdb_ID=3k3b ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | A series of tetrahydro-beta-carbolines were identified by HTS as inhibitors of the kinesin Eg5. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of removing potential metabolic liabilities and improving cellular potency. | ||
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| - | The discovery of tetrahydro-beta-carbolines as inhibitors of the kinesin Eg5.,Barsanti PA, Wang W, Ni ZJ, Duhl D, Brammeier N, Martin E, Bussiere D, Walter AO Bioorg Med Chem Lett. 2010 Jan 1;20(1):157-60. Epub 2009 Nov 12. PMID:19945875<ref>PMID:19945875</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3k3b" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Kinesin|Kinesin]] | + | *[[Kinesin 3D Structures|Kinesin 3D Structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Bellamacina C]] |
| - | [[Category: | + | [[Category: Bussiere DE]] |
| - | [[Category: | + | [[Category: Le V]] |
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Current revision
Co-crystal structure of the human kinesin Eg5 with a novel tetrahydro-beta-carboline
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