View source for 2uzq


==Protein Phosphatase, New Crystal Form==
<StructureSection load='2uzq' size='340' side='right'caption='[[2uzq]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uzq]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2UZQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cwr|1cwr]], [[1cws|1cws]], [[1cwt|1cwt]], [[1qb0|1qb0]], [[1ym9|1ym9]], [[1ymd|1ymd]], [[1ymk|1ymk]], [[1yml|1yml]], [[1ys0|1ys0]], [[2a2k|2a2k]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2uzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzq OCA], [http://pdbe.org/2uzq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2uzq RCSB], [http://www.ebi.ac.uk/pdbsum/2uzq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzq ProSAT]</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/2uzq_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=2uzq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cdc25 phosphatases are key activators of the eukaryotic cell cycle and compelling anticancer targets because their overexpression has been associated with numerous cancers. However, drug discovery targeting these phosphatases has been hampered by the lack of structural information about how Cdc25s interact with their native protein substrates, the cyclin-dependent kinases. Herein, we predict a docked orientation for Cdc25B with its Cdk2-pTpY-CycA protein substrate by a rigid-body docking method and refine the docked models with full-scale molecular dynamics simulations and minimization. We validate the stable ensemble structure experimentally by a variety of in vitro and in vivo techniques. Specifically, we compare our model with a crystal structure of the substrate-trapping mutant of Cdc25B. We identify and validate in vivo a novel hot-spot residue on Cdc25B (Arg492) that plays a central role in protein substrate recognition. We identify a hot-spot residue on the substrate Cdk2 (Asp206) and confirm its interaction with hot-spot residues on Cdc25 using hot-spot swapping and double mutant cycles to derive interaction energies. Our experimentally validated model is consistent with previous studies of Cdk2 and its interaction partners and initiates the opportunity for drug discovery of inhibitors that target the remote binding sites of this protein-protein interaction.

Experimental validation of the docking orientation of Cdc25 with its Cdk2-CycA protein substrate.,Sohn J, Parks JM, Buhrman G, Brown P, Kristjansdottir K, Safi A, Edelsbrunner H, Yang W, Rudolph J Biochemistry. 2005 Dec 20;44(50):16563-73. PMID:16342947<ref>PMID:16342947</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2uzq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]]
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Eberspaecher, U]]
[[Category: Hillig, R C]]
[[Category: Cell cycle]]
[[Category: Cell division]]
[[Category: Dual specificity]]
[[Category: Hydrolase]]
[[Category: Mitosis]]
[[Category: Phosphatase]]
[[Category: Phosphorylation]]
[[Category: Protein phosphatase]]