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== | ==P19INK4D/CDK6 COMPLEX== | ||
The crystal structure of the cyclin D-dependent kinase Cdk6 bound to the | <StructureSection load='1blx' size='340' side='right'caption='[[1blx]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1blx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BLX 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1blx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1blx OCA], [https://pdbe.org/1blx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1blx RCSB], [https://www.ebi.ac.uk/pdbsum/1blx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1blx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CDK6_HUMAN CDK6_HUMAN] Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans.<ref>PMID:8114739</ref> <ref>PMID:12833137</ref> <ref>PMID:14985467</ref> <ref>PMID:15254224</ref> <ref>PMID:15809340</ref> <ref>PMID:17431401</ref> <ref>PMID:17420273</ref> <ref>PMID:20668294</ref> <ref>PMID:20333249</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/bl/1blx_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=1blx ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The crystal structure of the cyclin D-dependent kinase Cdk6 bound to the p19 INK4d protein has been determined at 1.9 A resolution. The results provide the first structural information for a cyclin D-dependent protein kinase and show how the INK4 family of CDK inhibitors bind. The structure indicates that the conformational changes induced by p19INK4d inhibit both productive binding of ATP and the cyclin-induced rearrangement of the kinase from an inactive to an active conformation. The structure also shows how binding of an INK4 inhibitor would prevent binding of p27Kip1, resulting in its redistribution to other CDKs. Identification of the critical residues involved in the interaction explains how mutations in Cdk4 and p16INK4a result in loss of kinase inhibition and cancer. | |||
Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d.,Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ, Serrano M, Brenner SL, Blundell TL, Laue ED Nature. 1998 Sep 17;395(6699):244-50. PMID:9751051<ref>PMID:9751051</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 1blx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Archer SJ]] | |||
[[Category: Archer | [[Category: Blundell TL]] | ||
[[Category: Blundell | [[Category: Brenner SL]] | ||
[[Category: Brenner | [[Category: Brizuela L]] | ||
[[Category: Brizuela | [[Category: Brotherton DH]] | ||
[[Category: Brotherton | [[Category: Dhanaraj V]] | ||
[[Category: Dhanaraj | [[Category: Domaille PJ]] | ||
[[Category: Domaille | [[Category: Laue ED]] | ||
[[Category: Laue | [[Category: Parisini E]] | ||
[[Category: Parisini | [[Category: Serrano M]] | ||
[[Category: Serrano | [[Category: Smith BO]] | ||
[[Category: Smith | [[Category: Volyanik E]] | ||
[[Category: Volyanik | [[Category: Wick S]] | ||
[[Category: Wick | [[Category: Xu X]] | ||
[[Category: Xu | |||