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[[Image:1mx6.gif|left|200px]]


{{Structure
==Structure of p18INK4c (F92N)==
|PDB= 1mx6 |SIZE=350|CAPTION= <scene name='initialview01'>1mx6</scene>, resolution 2.0&Aring;
<StructureSection load='1mx6' size='340' side='right'caption='[[1mx6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
|SITE=
== Structural highlights ==
|LIGAND=
<table><tr><td colspan='2'>[[1mx6]] 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=1MX6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MX6 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
|GENE=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mx6 OCA], [https://pdbe.org/1mx6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mx6 RCSB], [https://www.ebi.ac.uk/pdbsum/1mx6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mx6 ProSAT]</span></td></tr>
}}
</table>
 
== Function ==
'''Structure of p18INK4c (F92N)'''
[https://www.uniprot.org/uniprot/CDN2C_HUMAN CDN2C_HUMAN] Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB.
 
== Evolutionary Conservation ==
 
[[Image:Consurf_key_small.gif|200px|right]]
==Overview==
Check<jmol>
p18(INK4c) is a member of the INK4 family of proteins that regulate the G(1) to S cell cycle transition by binding to and inhibiting the pRb kinase activity of cyclin-dependent kinases 4 and 6. The p16(INK4a) member of the INK4 protein family is altered in a variety of cancers and structure-function studies of the INK4 proteins reveal that the vast majority of missense tumor-derived p16(INK4a) mutations reduce protein thermodynamic stability. Based on this observation, we used p18(INK4c) as a model to test the proposal that INK4 proteins with increased stability might have enhanced cell cycle inhibitory activity. Structure-based mutagenesis was used to prepare p18(INK4c) mutant proteins with a predicted increase in stability. Using this approach, we report the generation of three mutant p18(INK4C) proteins, F71N, F82Q, and F92N, with increased stability toward thermal denaturation of which the F71N mutant also showed an increased stability to chemical denaturation. The x-ray crystal structures of the F71N, F82Q, and F92N p18INK4C mutant proteins were determined to reveal the structural basis for their increased stability properties. Significantly, the F71N mutant also showed enhanced CDK6 interaction and cell cycle inhibitory activity in vivo, as measured using co-immunoprecipitation and transient transfection assays, respectively. These studies show that a structure-based approach to increase the thermodynamic stability of INK4 proteins can be exploited to prepare more biologically active molecules with potential applications for the development of molecules to treat p16(INK4a)-mediated cancers.
  <jmolCheckbox>
 
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mx/1mx6_consurf.spt"</scriptWhenChecked>
==About this Structure==
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
1MX6 is a [[Single protein]] structure of sequence 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=1MX6 OCA].  
    <text>to colour the structure by Evolutionary Conservation</text>
 
  </jmolCheckbox>
==Reference==
</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=1mx6 ConSurf].
Structure-based design of p18INK4c proteins with increased thermodynamic stability and cell cycle inhibitory activity., Venkataramani RN, MacLachlan TK, Chai X, El-Deiry WS, Marmorstein R, J Biol Chem. 2002 Dec 13;277(50):48827-33. Epub 2002 Oct 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12370184 12370184]
<div style="clear:both"></div>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Chai, X.]]
[[Category: Chai X]]
[[Category: El-Deiry, W S.]]
[[Category: El-Deiry WS]]
[[Category: MacLachlan, T K.]]
[[Category: MacLachlan TK]]
[[Category: Marmorstein, R.]]
[[Category: Marmorstein R]]
[[Category: Venkataramani, R N.]]
[[Category: Venkataramani RN]]
[[Category: ankyrin repeat]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:49:19 2008''

Latest revision as of 07:49, 14 February 2024

Structure of p18INK4c (F92N)

1mx6, resolution 2.00Å

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