3hqd

From Proteopedia

(Difference between revisions)

Revision as of 07:34, 12 December 2018

Human kinesin Eg5 motor domain in complex with AMPPNP and Mg2+

Structural highlights

3hqd 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, 1x88, 1q0b, 2ieh
Gene:	EG5, KIF11, KNSL1, TRIP5 (HUMAN)
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

Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin.AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for gamma-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.

ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism.,Parke CL, Wojcik EJ, Kim S, Worthylake DK J Biol Chem. 2010 Feb 19;285(8):5859-67. Epub 2009 Dec 15. PMID:20018897^[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
↑ Parke CL, Wojcik EJ, Kim S, Worthylake DK. ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism. J Biol Chem. 2010 Feb 19;285(8):5859-67. Epub 2009 Dec 15. PMID:20018897 doi:10.1074/jbc.M109.071233

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/3hqd"

@@ Line 1: / Line 1: @@
 ==Human kinesin Eg5 motor domain in complex with AMPPNP and Mg2+==
 <StructureSection load='3hqd' size='340' side='right' caption='[[3hqd]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ii6|1ii6]], [[1x88|1x88]], [[1q0b|1q0b]], [[2ieh|2ieh]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EG5, KIF11, KNSL1, TRIP5 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hqd OCA], [http://pdbe.org/3hqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hqd RCSB], [http://www.ebi.ac.uk/pdbsum/3hqd PDBsum]</span></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=3hqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hqd OCA], [http://pdbe.org/3hqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hqd RCSB], [http://www.ebi.ac.uk/pdbsum/3hqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hqd ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hq/3hqd_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hq/3hqd_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 47: / Line 48: @@
 [[Category: Cell cycle]]
 [[Category: Cell division]]
+[[Category: Coiled coil]]
 [[Category: Kinesin]]
 [[Category: Microtubule]]
@@ Line 54: / Line 56: @@
 [[Category: Nucleotide-binding]]
 [[Category: Phosphoprotein]]
+[[Category: Polymorphism]]
 [[Category: Spindle protein]]

3hqd

From Proteopedia

Revision as of 07:34, 12 December 2018

Human kinesin Eg5 motor domain in complex with AMPPNP and Mg2+

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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