2uzq: Difference between revisions

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<StructureSection load='2uzq' size='340' side='right'caption='[[2uzq]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
<StructureSection load='2uzq' size='340' side='right'caption='[[2uzq]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2uzq]] is a 6 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=2UZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UZQ FirstGlance]. <br>
<table><tr><td colspan='2'>[[2uzq]] is a 6 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=2UZQ OCA]. For a <b>guided tour on the structure components</b> use [https://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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cwr|1cwr]], [[1cws|1cws]], [[1cwt|1cwt]], [[1qb0|1qb0]], [[1ym9|1ym9]], [[1ymd|1ymd]], [[1ymk|1ymk]], [[1yml|1yml]], [[1ys0|1ys0]], [[2a2k|2a2k]]</div></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='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=2uzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzq OCA], [https://pdbe.org/2uzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uzq RCSB], [https://www.ebi.ac.uk/pdbsum/2uzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzq ProSAT]</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=2uzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzq OCA], [https://pdbe.org/2uzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uzq RCSB], [https://www.ebi.ac.uk/pdbsum/2uzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzq ProSAT]</span></td></tr>
</table>
</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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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].
</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="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==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Eberspaecher U]]
[[Category: Eberspaecher, U]]
[[Category: Hillig RC]]
[[Category: Hillig, R C]]
[[Category: Cell cycle]]
[[Category: Cell division]]
[[Category: Dual specificity]]
[[Category: Hydrolase]]
[[Category: Mitosis]]
[[Category: Phosphatase]]
[[Category: Phosphorylation]]
[[Category: Protein phosphatase]]

Latest revision as of 17:59, 13 December 2023

Protein Phosphatase, New Crystal FormProtein Phosphatase, New Crystal Form

Structural highlights

2uzq is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.38Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Schmidt A, Durgan J, Magalhaes A, Hall A. Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis. EMBO J. 2007 Mar 21;26(6):1624-36. Epub 2007 Mar 1. PMID:17332740 doi:http://dx.doi.org/10.1038/sj.emboj.7601637

2uzq, resolution 2.38Å

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