2q2y: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal Structure of KSP in complex with Inhibitor 1== | ==Crystal Structure of KSP in complex with Inhibitor 1== | ||
<StructureSection load='2q2y' size='340' side='right' caption='[[2q2y]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2q2y' size='340' side='right'caption='[[2q2y]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2q2y]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2q2y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q2Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q2Y 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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MKR:1-{(3R,3AR)-3-[3-(4-ACETYLPIPERAZIN-1-YL)PROPYL]-8-FLUORO-3-PHENYL-3A,4-DIHYDRO-3H-PYRAZOLO[5,1-C][1,4]BENZOXAZIN-2-YL}ETHANONE'>MKR</scene></td></tr> | </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=MKR:1-{(3R,3AR)-3-[3-(4-ACETYLPIPERAZIN-1-YL)PROPYL]-8-FLUORO-3-PHENYL-3A,4-DIHYDRO-3H-PYRAZOLO[5,1-C][1,4]BENZOXAZIN-2-YL}ETHANONE'>MKR</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q2z|2q2z]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2q2z|2q2z]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIF11, EG5, KNSL1, TRIP5 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIF11, EG5, KNSL1, TRIP5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2q2y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q2y OCA], [https://pdbe.org/2q2y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q2y RCSB], [https://www.ebi.ac.uk/pdbsum/2q2y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q2y 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]] | ||
| Line 34: | Line 34: | ||
==See Also== | ==See Also== | ||
*[[Kinesin|Kinesin]] | *[[Kinesin 3D Structures|Kinesin 3D Structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 40: | Line 40: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Yan, Y]] | [[Category: Yan, Y]] | ||
[[Category: Cell cycle]] | [[Category: Cell cycle]] | ||
[[Category: Ksp]] | [[Category: Ksp]] | ||
[[Category: Ksp-inhibitor complex]] | [[Category: Ksp-inhibitor complex]] | ||
Revision as of 11:06, 25 June 2021
Crystal Structure of KSP in complex with Inhibitor 1Crystal Structure of KSP in complex with Inhibitor 1
Structural highlights
Disease[KIF11_HUMAN] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM: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.[1] Function[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.[2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInspired by previous efforts in the pyrazolobenzoxazine class of KSP inhibitors, the design and synthesis of 1,4-diaryl-4,5-dihydropyrazole inhibitors of KSP are described. Crystallographic evidence of binding mode and in vivo potency data is also highlighted. Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.,Roecker AJ, Coleman PJ, Mercer SP, Schreier JD, Buser CA, Walsh ES, Hamilton K, Lobell RB, Tao W, Diehl RE, South VJ, Davide JP, Kohl NE, Yan Y, Kuo LC, Li C, Fernandez-Metzler C, Mahan EA, Prueksaritanont T, Hartman GD Bioorg Med Chem Lett. 2007 Oct 15;17(20):5677-82. Epub 2007 Aug 21. PMID:17766111[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||