View source for 2uzr

==A TRANSFORMING MUTATION IN THE PLECKSTRIN HOMOLOGY DOMAIN OF AKT1 IN CANCER (AKT1-PH_E17K)==
<StructureSection load='2uzr' size='340' side='right' caption='[[2uzr]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uzr]] is a 1 chain structure with 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=2UZR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UZR FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h10|1h10]], [[1unp|1unp]], [[1unq|1unq]], [[1unr|1unr]], [[2uvm|2uvm]], [[2uzs|2uzs]]</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2uzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2uzr RCSB], [http://www.ebi.ac.uk/pdbsum/2uzr PDBsum]</span></td></tr>
<table>
== 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/uz/2uzr_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development.

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer.,Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S, Uhlik M, Lin A, Du J, Qian YW, Zeckner DJ, Tucker-Kellogg G, Touchman J, Patel K, Mousses S, Bittner M, Schevitz R, Lai MH, Blanchard KL, Thomas JE Nature. 2007 Jul 26;448(7152):439-44. Epub 2007 Jul 4. PMID:17611497<ref>PMID:17611497</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Bittner, M.]]
[[Category: Blanchard, K L.]]
[[Category: Boguslawski, S.]]
[[Category: Briggs, S L.]]
[[Category: Carpten, J D.]]
[[Category: Donoho, G P.]]
[[Category: Du, J.]]
[[Category: Faber, A L.]]
[[Category: Horn, C.]]
[[Category: Hostetter, G.]]
[[Category: Lai, M H.]]
[[Category: Lin, A.]]
[[Category: Moses, T Y.]]
[[Category: Mousses, S.]]
[[Category: Patel, K.]]
[[Category: Qian, Y W.]]
[[Category: Robbins, C M.]]
[[Category: Savage, S.]]
[[Category: Schevitz, R.]]
[[Category: Thomas, J E.]]
[[Category: Touchman, J.]]
[[Category: Tucker-Kellogg, G.]]
[[Category: Uhlik, M.]]
[[Category: Zeckner, D J.]]
[[Category: Apoptosis]]
[[Category: Atp-binding]]
[[Category: Carbohydrate metabolism]]
[[Category: Glucose metabolism]]
[[Category: Glycogen biosynthesis]]
[[Category: Glycogen metabolism]]
[[Category: Kinase]]
[[Category: Nuclear protein]]
[[Category: Nucleotide- binding]]
[[Category: Phosphorylation]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Sugar transport]]
[[Category: Transferase]]
[[Category: Translation regulation]]
[[Category: Transport]]