3dw8: Difference between revisions

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== Structural highlights ==

<table><tr><td colspan='2'>[[3dw8]] is a 8 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=3DW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DW8 FirstGlance]. <br>

<table><tr><td colspan='2'>[[3dw8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Cyanobacteria Cyanobacteria] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DW8 FirstGlance]. <br>

</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>~~</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]] 2.85Å</td></tr>

<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=1ZN:(2S,3S,4E,6E,8S,9S)-3-AMINO-9-METHOXY-2,6,8-TRIMETHYL-10-PHENYLDECA-4,6-DIENOIC+ACID'>1ZN</scene>, <scene name='pdbligand=ACB:3-METHYL-BETA-D-ASPARTIC+ACID'>ACB</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAM:N-METHYL-ALPHA-BETA-DEHYDROALANINE'>DAM</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene><~~/td></tr>~~

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1ZN:(2S,3S,4E,6E,8S,9S)-3-AMINO-9-METHOXY-2,6,8-TRIMETHYL-10-PHENYLDECA-4,6-DIENOIC+ACID'>1ZN</scene>, <scene name='pdbligand=ACB:3-METHYL-BETA-D-ASPARTIC+ACID'>ACB</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAM:N-METHYL-ALPHA-BETA-DEHYDROALANINE'>DAM</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>

~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene|Gene~~:~~]]</b></td><td class="sblockDat">PPP2R1A~~ (~~[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]~~), PPP2R2A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PPP2CA ([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/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=3dw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dw8 OCA], [https://pdbe.org/3dw8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dw8 RCSB], [https://www.ebi.ac.uk/pdbsum/3dw8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dw8 ProSAT]</span></td></tr>

</table>

== Function ==

[[https://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN]] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</ref> [[https://www.uniprot.org/uniprot/PP2AA_HUMAN PP2AA_HUMAN]] PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.<ref>PMID:9920888</ref> <ref>PMID:10801873</ref> <ref>PMID:22613722</ref> [[https://www.uniprot.org/uniprot/2ABA_HUMAN 2ABA_HUMAN]] The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.

[https://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</ref>

== Evolutionary Conservation ==

[[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=3dw8 ConSurf].

~~<div style="background-color:#fffaf0;">~~

~~== Publication Abstract from PubMed ==~~

Protein phosphatase 2A (PP2A) regulates many essential aspects of cellular physiology. Members of the regulatory B/B55/PR55 family are thought to play a key role in the dephosphorylation of Tau, whose hyperphosphorylation contributes to Alzheimer's disease. The underlying mechanisms of the PP2A-Tau connection remain largely enigmatic. Here, we report the complete reconstitution of a Tau dephosphorylation assay and the crystal structure of a heterotrimeric PP2A holoenzyme involving the regulatory subunit Balpha. We show that Balpha specifically and markedly facilitates dephosphorylation of the phosphorylated Tau in our reconstituted assay. The Balpha subunit comprises a seven-bladed beta propeller, with an acidic, substrate-binding groove located in the center of the propeller. The beta propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding beta hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau.

Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation.,Xu Y, Chen Y, Zhang P, Jeffrey PD, Shi Y Mol Cell. 2008 Sep 26;31(6):873-85. PMID:18922469<ref>PMID:18922469</ref>

~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~

~~</div>~~

~~<div class="pdbe-citations 3dw8" style="background-color:#fffaf0;"></div>~~

==See Also==

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__TOC__

</StructureSection>

[[Category: ~~Human~~]]

[[Category: Cyanobacteria]]

[[Category: Homo sapiens]]

[[Category: Large Structures]]

~~[[Category: Phosphoprotein phosphatase]]~~

[[Category: Chen Y]]

[[Category: Chen, Y]]

[[Category: Jeffrey PD]]

[[Category: Jeffrey~~, P D~~]]

[[Category: Shi Y]]

[[Category: Shi, Y]]

[[Category: Xu Y]]

[[Category: Xu, Y]]

[[Category: Zhang P]]

[[Category: Zhang, P]]

~~[[Category: B55]]~~

~~[[Category: Holoenzyme]]~~

~~[[Category: Hydrolase]]~~

~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~

~~[[Category: Iron]]~~

~~[[Category: Manganese]]~~

~~[[Category: Metal-binding]]~~

~~[[Category: Methylation]]~~

~~[[Category: Phosphoprotein]]~~

~~[[Category: Pr55]]~~

~~[[Category: Protein phosphatase]]~~

~~[[Category: Wd repeat~~]]

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@@ Line 3: / Line 3: @@
 <StructureSection load='3dw8' size='340' side='right'caption='[[3dw8]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3dw8]] is a 8 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=3DW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DW8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3dw8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Cyanobacteria Cyanobacteria] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DW8 FirstGlance]. <br>
-</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></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]] 2.85&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1ZN:(2S,3S,4E,6E,8S,9S)-3-AMINO-9-METHOXY-2,6,8-TRIMETHYL-10-PHENYLDECA-4,6-DIENOIC+ACID'>1ZN</scene>, <scene name='pdbligand=ACB:3-METHYL-BETA-D-ASPARTIC+ACID'>ACB</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAM:N-METHYL-ALPHA-BETA-DEHYDROALANINE'>DAM</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1ZN:(2S,3S,4E,6E,8S,9S)-3-AMINO-9-METHOXY-2,6,8-TRIMETHYL-10-PHENYLDECA-4,6-DIENOIC+ACID'>1ZN</scene>, <scene name='pdbligand=ACB:3-METHYL-BETA-D-ASPARTIC+ACID'>ACB</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAM:N-METHYL-ALPHA-BETA-DEHYDROALANINE'>DAM</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP2R1A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PPP2R2A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PPP2CA ([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/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=3dw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dw8 OCA], [https://pdbe.org/3dw8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dw8 RCSB], [https://www.ebi.ac.uk/pdbsum/3dw8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dw8 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN]] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</ref>  [[https://www.uniprot.org/uniprot/PP2AA_HUMAN PP2AA_HUMAN]] PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.<ref>PMID:9920888</ref> <ref>PMID:10801873</ref> <ref>PMID:22613722</ref>  [[https://www.uniprot.org/uniprot/2ABA_HUMAN 2ABA_HUMAN]] The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.
+[https://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 22: / Line 20: @@
 </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=3dw8 ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Protein phosphatase 2A (PP2A) regulates many essential aspects of cellular physiology. Members of the regulatory B/B55/PR55 family are thought to play a key role in the dephosphorylation of Tau, whose hyperphosphorylation contributes to Alzheimer's disease. The underlying mechanisms of the PP2A-Tau connection remain largely enigmatic. Here, we report the complete reconstitution of a Tau dephosphorylation assay and the crystal structure of a heterotrimeric PP2A holoenzyme involving the regulatory subunit Balpha. We show that Balpha specifically and markedly facilitates dephosphorylation of the phosphorylated Tau in our reconstituted assay. The Balpha subunit comprises a seven-bladed beta propeller, with an acidic, substrate-binding groove located in the center of the propeller. The beta propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding beta hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau.
-Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation.,Xu Y, Chen Y, Zhang P, Jeffrey PD, Shi Y Mol Cell. 2008 Sep 26;31(6):873-85. PMID:18922469<ref>PMID:18922469</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 3dw8" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 38: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Cyanobacteria]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Phosphoprotein phosphatase]]
+[[Category: Chen Y]]
-[[Category: Chen, Y]]
+[[Category: Jeffrey PD]]
-[[Category: Jeffrey, P D]]
+[[Category: Shi Y]]
-[[Category: Shi, Y]]
+[[Category: Xu Y]]
-[[Category: Xu, Y]]
+[[Category: Zhang P]]
-[[Category: Zhang, P]]
-[[Category: B55]]
-[[Category: Holoenzyme]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Iron]]
-[[Category: Manganese]]
-[[Category: Metal-binding]]
-[[Category: Methylation]]
-[[Category: Phosphoprotein]]
-[[Category: Pr55]]
-[[Category: Protein phosphatase]]
-[[Category: Wd repeat]]