1bi7: Difference between revisions

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-[[Image:1bi7.gif|left|200px]]
-<!--
+==MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX==
-The line below this paragraph, containing "STRUCTURE_1bi7", creates the "Structure Box" on the page.
+<StructureSection load='1bi7' size='340' side='right'caption='[[1bi7]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1bi7]] 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=1BI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BI7 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</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=1bi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bi7 OCA], [https://pdbe.org/1bi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bi7 RCSB], [https://www.ebi.ac.uk/pdbsum/1bi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bi7 ProSAT]</span></td></tr>
-{{STRUCTURE_1bi7|  PDB=1bi7  |  SCENE=  }}
+</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/bi/1bi7_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=1bi7 ConSurf].
+<div style="clear:both"></div>
-'''MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX'''
+==See Also==
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
+== References ==
-==Overview==
+<references/>
-The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16INK4a tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next to the ATP-binding site of the catalytic cleft, opposite where the activating cyclin subunit binds. They prevent cyclin binding indirectly by causing structural changes that propagate to the cyclin-binding site. The INK4 inhibitors also distort the kinase catalytic cleft and interfere with ATP binding, which explains how they can inhibit the preassembled Cdk4/6-cyclin D complexes as well. Tumour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a.
+__TOC__
+</StructureSection>
-==About this Structure==
-BI7 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BI7 OCA].
-==Reference==
-Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a., Russo AA, Tong L, Lee JO, Jeffrey PD, Pavletich NP, Nature. 1998 Sep 17;395(6699):237-43. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9751050 9751050]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Jeffrey, P D.]]
+[[Category: Jeffrey PD]]
-[[Category: Lee, J O.]]
+[[Category: Lee JO]]
-[[Category: Pavletich, N P.]]
+[[Category: Pavletich NP]]
-[[Category: Russo, A A.]]
+[[Category: Russo AA]]
-[[Category: Tong, L.]]
+[[Category: Tong L]]
-[[Category: Cdk]]
-[[Category: Cell cycle]]
-[[Category: Cyclin dependent kinase]]
-[[Category: Cyclin dependent kinase inhibitory protein]]
-[[Category: Ink4]]
-[[Category: Mts1]]
-[[Category: Multiple tumor suppressor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 11:32:38 2008''