View source for 6alz


==Crystal structure of Protein Phosphatase 1 bound to the natural inhibitor Tautomycetin==
<StructureSection load='6alz' size='340' side='right'caption='[[6alz]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6alz]] 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=6ALZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ALZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.208&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BKM:(~{Z})-2-[(1~{R})-3-[(2~{R},3~{S},4~{R},7~{S},8~{S},11~{S},13~{R},16~{E})-17-ethyl-3,7,11,13-tetramethyl-4,8-bis(oxidanyl)-6,15-bis(oxidanylidene)nonadeca-16,18-dien-2-yl]oxy-1-oxidanyl-3-oxidanylidene-propyl]-3-methyl-but-2-enedioic+acid'>BKM</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=6alz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6alz OCA], [https://pdbe.org/6alz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6alz RCSB], [https://www.ebi.ac.uk/pdbsum/6alz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6alz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PP1A_HUMAN PP1A_HUMAN] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.<ref>PMID:17283141</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Selective inhibitors for each serine/threonine phosphatase (PPP) are essential to investigate the biological actions of PPPs and to guide drug development. Biologically diverse organisms (e.g., cyanobacteria, dinoflagellates, beetles) produce structurally distinct toxins that are catalytic inhibitors of PPPs. However, most toxins exhibit little selectivity, typically inhibiting multiple family members with similar potencies. Thus, the use of these toxins as chemical tools to study the relationship between individual PPPs and their biological substrates, and how disruptions in these relationships contributes to human disease, is severely limited. Here, we show that tautomycetin (TTN) is highly selective for a single PPP, protein phosphatase 1 (PP1/PPP1C). Our structure of the PP1:TTN complex reveals that PP1 selectivity is defined by a covalent bond between TTN and a PP1-specific cysteine residue, Cys127. Together, these data provide key molecular insights needed for the development of novel probes targeting single PPPs, especially PP1.

PP1:Tautomycetin Complex Reveals a Path toward the Development of PP1-Specific Inhibitors.,Choy MS, Swingle M, D'Arcy B, Abney K, Rusin SF, Kettenbach AN, Page R, Honkanen RE, Peti W J Am Chem Soc. 2017 Nov 28. doi: 10.1021/jacs.7b09368. PMID:29156132<ref>PMID:29156132</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6alz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Choy MS]]
[[Category: Page R]]
[[Category: Peti W]]