2uym

From Proteopedia

(Difference between revisions)

Revision as of 11:14, 17 June 2020

Crystal structure of KSP in complex with ADP and thiophene containing inhibitor 37

Structural highlights

2uym is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1ii6, 1q0b, 1x88, 1yrs, 2fky, 2fl2, 2fl6, 2g1q, 2gm1, 2uyi
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

We have identified and synthesized a series of thiophene containing inhibitors of kinesin spindle protein. SAR studies led to the synthesis of 33, which was co-crystallized with KSP and determined to bind to an allosteric pocket previously described for other known KSP inhibitors.

Synthesis and SAR of thiophene containing kinesin spindle protein (KSP) inhibitors.,Pinkerton AB, Lee TT, Hoffman TZ, Wang Y, Kahraman M, Cook TG, Severance D, Gahman TC, Noble SA, Shiau AK, Davis RL Bioorg Med Chem Lett. 2007 Jul 1;17(13):3562-9. Epub 2007 Apr 29. PMID:17498954^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, van Impel A, Moore AT, Loeys BL, Ghalamkarpour A, Onoufriadis A, Martinez-Corral I, Devery S, Leroy JG, van Laer L, Singer A, Bialer MG, McEntagart M, Quarrell O, Brice G, Trembath RC, Schulte-Merker S, Makinen T, Vikkula M, Mortimer PS, Mansour S, Jeffery S. Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet. 2012 Feb 10;90(2):356-62. doi: 10.1016/j.ajhg.2011.12.018. Epub, 2012 Jan 26. PMID:22284827 doi:10.1016/j.ajhg.2011.12.018
↑ Rapley J, Nicolas M, Groen A, Regue L, Bertran MT, Caelles C, Avruch J, Roig J. The NIMA-family kinase Nek6 phosphorylates the kinesin Eg5 at a novel site necessary for mitotic spindle formation. J Cell Sci. 2008 Dec 1;121(Pt 23):3912-21. doi: 10.1242/jcs.035360. Epub 2008 Nov, 11. PMID:19001501 doi:10.1242/jcs.035360
↑ Pinkerton AB, Lee TT, Hoffman TZ, Wang Y, Kahraman M, Cook TG, Severance D, Gahman TC, Noble SA, Shiau AK, Davis RL. Synthesis and SAR of thiophene containing kinesin spindle protein (KSP) inhibitors. Bioorg Med Chem Lett. 2007 Jul 1;17(13):3562-9. Epub 2007 Apr 29. PMID:17498954 doi:10.1016/j.bmcl.2007.04.076

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2uym"

@@ Line 1: / Line 1: @@
 ==Crystal structure of KSP in complex with ADP and thiophene containing inhibitor 37==
-<StructureSection load='2uym' size='340' side='right' caption='[[2uym]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
+<StructureSection load='2uym' size='340' side='right'caption='[[2uym]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2uym]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UYM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UYM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2uym]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UYM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2UYM 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=K03:N,N-DIETHYL-5,5-DIMETHYL-2-[(2-THIENYLCARBONYL)AMINO]-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE'>K03</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=K03:N,N-DIETHYL-5,5-DIMETHYL-2-[(2-THIENYLCARBONYL)AMINO]-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE'>K03</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ii6|1ii6]], [[1q0b|1q0b]], [[1x88|1x88]], [[1yrs|1yrs]], [[2fky|2fky]], [[2fl2|2fl2]], [[2fl6|2fl6]], [[2g1q|2g1q]], [[2gm1|2gm1]], [[2uyi|2uyi]]</td></tr>
-<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=2uym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uym OCA], [http://pdbe.org/2uym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2uym RCSB], [http://www.ebi.ac.uk/pdbsum/2uym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2uym ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2uym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uym OCA], [http://pdbe.org/2uym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2uym RCSB], [http://www.ebi.ac.uk/pdbsum/2uym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2uym ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 33: / Line 33: @@
 ==See Also==
-*[[Kinesin|Kinesin]]
+*[[Kinesin 3D Structures|Kinesin 3D Structures]]
 == References ==
 <references/>
@@ Line 39: / Line 39: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Lee, T T]]
 [[Category: Atp-binding]]

2uym

From Proteopedia

Revision as of 11:14, 17 June 2020

Crystal structure of KSP in complex with ADP and thiophene containing inhibitor 37

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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