2fl6: Difference between revisions

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OCA

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-[[Image:2fl6.gif|left|200px]]<br />
-<applet load="2fl6" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2fl6, resolution 2.5&Aring;" />
-'''crystal structure of KSP in complex with inhibitor 6'''<br />
-==Overview==
+==crystal structure of KSP in complex with inhibitor 6==
-The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is, described. Introduction of basic amide and urea moieties to the, dihydropyrrole nucleus enhanced potency and aqueous solubility, simultaneously, and provided compounds that caused mitotic arrest of A2780, human ovarian carcinoma cells with EC(50)s&lt;10nM. Ancillary hERG activity, was evaluated for this series of inhibitors.
+<StructureSection load='2fl6' size='340' side='right'caption='[[2fl6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2fl6]] 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=2FL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FL6 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]] 2.5&#8491;</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N5T:(2S)-4-(2,5-DIFLUOROPHENYL)-N,N-DIMETHYL-2-PHENYL-2,5-DIHYDRO-1H-PYRROLE-1-CARBOXAMIDE'>N5T</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=2fl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fl6 OCA], [https://pdbe.org/2fl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fl6 RCSB], [https://www.ebi.ac.uk/pdbsum/2fl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fl6 ProSAT]</span></td></tr>
+</table>
+== 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 ==
+[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 ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fl/2fl6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2fl6 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-FL6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, ADP and N5T as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FL6 OCA].
+*[[Kinesin 3D Structures|Kinesin 3D Structures]]
+== References ==
-==Reference==
+<references/>
-Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP., Fraley ME, Garbaccio RM, Arrington KL, Hoffman WF, Tasber ES, Coleman PJ, Buser CA, Walsh ES, Hamilton K, Fernandes C, Schaber MD, Lobell RB, Tao W, South VJ, Yan Y, Kuo LC, Prueksaritanont T, Shu C, Torrent M, Heimbrook DC, Kohl NE, Huber HE, Hartman GD, Bioorg Med Chem Lett. 2006 Apr 1;16(7):1775-9. Epub 2006 Jan 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16439123 16439123]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Yan, Y.]]
+[[Category: Yan Y]]
-[[Category: ADP]]
-[[Category: MG]]
-[[Category: N5T]]
-[[Category: ksp]]
-[[Category: ksp-inhibitor complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:06:54 2007''