View source for 2ifv


==Crystal structure of an active site mutant, C473D, of CDC25B phosphatase catalytic domain==
<StructureSection load='2ifv' size='340' side='right'caption='[[2ifv]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ifv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IFV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IFV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ymk|1ymk]], [[1qb0|1qb0]], [[2a2k|2a2k]], [[2ifd|2ifd]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC25B, CDC25HU2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2ifv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ifv OCA], [https://pdbe.org/2ifv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ifv RCSB], [https://www.ebi.ac.uk/pdbsum/2ifv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ifv ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/MPIP2_HUMAN MPIP2_HUMAN]] Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Directly dephosphorylates CDK1 and stimulates its kinase activity. The three isoforms seem to have a different level of activity.<ref>PMID:17332740</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/if/2ifv_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=2ifv ConSurf].
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== Publication Abstract from PubMed ==
Using a combination of steady-state and single-turnover kinetics, we probe substrate association, dissociation, and chemistry for the reaction of Cdc25B phosphatase with its Cdk2-pTpY/CycA protein substrate. The rate constant for substrate association for the wild-type enzyme is 1.3 x 10(6) M(-1) s(-1). The rate constant for dissociation is slow compared to the rate constant for phosphate transfer to form the phospho-enzyme intermediate (k2 = 1.1 s(-1)), making Cdk2-pTpY/CycA a sticky substrate. Compared to the wild type, all hotspot mutants of residues at the remote docking site that specifically affect catalysis with the protein substrate (Arg488, Arg492, and Tyr497 on Cdc25B and Asp206 on Cdk2) have greatly slowed rate constants of association (70- to 4500-fold), and some mutants have decreased k2 values compared to that of the wild type. Most dramatically, R492L, despite showing no significant changes in a crystal structure at 2.0 A resolution, has an approximately 100-fold decrease in k2 compared to that of wild-type Cdc25B. The active site C473S mutant binds tightly to and dissociates slowly from Cdk2-pTpY/CycA (Kd = 10 nM, k(off) = 0.01 s(-1)). In contrast, the C473D mutant, despite showing only localized perturbations in the active site at 1.6 A resolution, has a much weaker affinity and dissociates rapidly (Kd of 2 microM, k(off) &gt; 2 s(-1)) from the protein substrate. Overall, we demonstrate that the association of Cdc25B with its Cdk2-pTpY/CycA substrate is governed to a significant extent by the interactions of the remote hotspot residues, whereas dissociation is governed by interactions at the active site.

Kinetic and structural studies of specific protein-protein interactions in substrate catalysis by Cdc25B phosphatase.,Sohn J, Buhrman G, Rudolph J Biochemistry. 2007 Jan 23;46(3):807-18. PMID:17223702<ref>PMID:17223702</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2ifv" 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: Buhrman, G]]
[[Category: Rudolph, J]]
[[Category: Active site mutant]]
[[Category: Dual specificity]]
[[Category: Hydrolase]]
[[Category: Phosphatase]]