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< | ==Catalytic domain of human Serine/Threonine Phosphatase 5 (PP5c) with two Mn2+ atoms originally soaked with cantharidin (which is present in the structure in the hydrolyzed form)== | ||
<StructureSection load='3h63' size='340' side='right'caption='[[3h63]], [[Resolution|resolution]] 1.30Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3h63]] 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=3H63 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H63 FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NHC:(1R,2S,3R,4S)-2,3-DIMETHYL-7-OXABICYCLO[2.2.1]HEPTANE-2,3-DICARBOXYLIC+ACID'>NHC</scene></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=3h63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h63 OCA], [https://pdbe.org/3h63 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h63 RCSB], [https://www.ebi.ac.uk/pdbsum/3h63 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h63 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PPP5_HUMAN PPP5_HUMAN] May play a role in the regulation of RNA biogenesis and/or mitosis. In vitro, dephosphorylates serine residues of skeletal muscle phosphorylase and histone H1. | |||
== 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/h6/3h63_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=3h63 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The inhibition of a subgroup of human serine/threonine protein phosphatases is responsible for the cytotoxicity of cantharidin and norcantharidin against tumor cells. It is shown that the anhydride rings of cantharidin and norcantharidin are hydrolyzed when bound to the catalytic domain of the human serine/threonine protein phosphatases 5 (PP5c), and the high-resolution crystal structures of PP5c complexed with the corresponding dicarboxylic acid derivatives of the two molecules are reported. Norcantharidin shows a unique binding conformation with the catalytically active Mn2PP5c, while cantharidin is characterized by a double conformation in its binding mode to the protein. Different binding modes of norcantharidin are observed depending of whether the starting ligand is in the anhydride or in the dicarboxylic acid form. All these structures will provide the basis for the rational design of new cantharidin-based drugs. | |||
Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin.,Bertini I, Calderone V, Fragai M, Luchinat C, Talluri E J Med Chem. 2009 Aug 13;52(15):4838-43. PMID:19601647<ref>PMID:19601647</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3h63" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bertini | [[Category: Bertini I]] | ||
[[Category: Calderone | [[Category: Calderone V]] | ||
[[Category: Fragai | [[Category: Fragai M]] | ||
[[Category: Luchinat | [[Category: Luchinat C]] | ||
[[Category: Talluri | [[Category: Talluri E]] | ||
Latest revision as of 18:47, 1 November 2023
Catalytic domain of human Serine/Threonine Phosphatase 5 (PP5c) with two Mn2+ atoms originally soaked with cantharidin (which is present in the structure in the hydrolyzed form)Catalytic domain of human Serine/Threonine Phosphatase 5 (PP5c) with two Mn2+ atoms originally soaked with cantharidin (which is present in the structure in the hydrolyzed form)
Structural highlights
FunctionPPP5_HUMAN May play a role in the regulation of RNA biogenesis and/or mitosis. In vitro, dephosphorylates serine residues of skeletal muscle phosphorylase and histone H1. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe inhibition of a subgroup of human serine/threonine protein phosphatases is responsible for the cytotoxicity of cantharidin and norcantharidin against tumor cells. It is shown that the anhydride rings of cantharidin and norcantharidin are hydrolyzed when bound to the catalytic domain of the human serine/threonine protein phosphatases 5 (PP5c), and the high-resolution crystal structures of PP5c complexed with the corresponding dicarboxylic acid derivatives of the two molecules are reported. Norcantharidin shows a unique binding conformation with the catalytically active Mn2PP5c, while cantharidin is characterized by a double conformation in its binding mode to the protein. Different binding modes of norcantharidin are observed depending of whether the starting ligand is in the anhydride or in the dicarboxylic acid form. All these structures will provide the basis for the rational design of new cantharidin-based drugs. Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin.,Bertini I, Calderone V, Fragai M, Luchinat C, Talluri E J Med Chem. 2009 Aug 13;52(15):4838-43. PMID:19601647[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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