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1u32

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Revision as of 07:19, 30 December 2020

Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid

Structural highlights

1u32 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	PPP1CC (HUMAN)
Activity:	Phosphoprotein phosphatase, with EC number 3.1.3.16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PP1G_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. Dephosphorylates RPS6KB1. 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.^[1] ^[2]

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 PubMed

Protein phosphatase-1 and protein phosphatase-2B (calcineurin) are eukaryotic serine/threonine phosphatases that share 40% sequence identity in their catalytic subunits. Despite the similarities in sequence, these phosphatases are widely divergent when it comes to inhibition by natural product toxins, such as microcystin-LR and okadaic acid. The most prominent region of non-conserved sequence between these phosphatases corresponds to the beta12-beta13 loop of protein phosphatase-1, and the L7 loop of toxin-resistant calcineurin. In the present study, mutagenesis of residues 273-277 of the beta12-beta13 loop of the protein phosphatase-1 catalytic subunit (PP-1c) to the corresponding residues in calcineurin (312-316), resulted in a chimeric mutant that showed a decrease in sensitivity to microcystin-LR, okadaic acid, and the endogenous PP-1c inhibitor protein inhibitor-2. A crystal structure of the chimeric mutant in complex with okadaic acid was determined to 2.0-A resolution. The beta12-beta13 loop region of the mutant superimposes closely with that of wild-type PP-1c bound to okadaic acid. Systematic mutation of each residue in the beta12-beta13 loop of PP-1c showed that a single amino acid change (C273L) was the most influential in mediating sensitivity of PP-1c to toxins. Taken together, these data indicate that it is an individual amino acid residue substitution and not a change in the overall beta12-beta13 loop conformation of protein phosphatase-1 that contributes to disrupting important interactions with inhibitors such as microcystin-LR and okadaic acid.

Crystal structure and mutagenesis of a protein phosphatase-1:calcineurin hybrid elucidate the role of the beta12-beta13 loop in inhibitor binding.,Maynes JT, Perreault KR, Cherney MM, Luu HA, James MN, Holmes CF J Biol Chem. 2004 Oct 8;279(41):43198-206. Epub 2004 Jul 26. PMID:15280359^[3]

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

References

↑ Djouder N, Metzler SC, Schmidt A, Wirbelauer C, Gstaiger M, Aebersold R, Hess D, Krek W. S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Mol Cell. 2007 Oct 12;28(1):28-40. PMID:17936702 doi:http://dx.doi.org/10.1016/j.molcel.2007.08.010
↑ Lee JH, You J, Dobrota E, Skalnik DG. Identification and characterization of a novel human PP1 phosphatase complex. J Biol Chem. 2010 Aug 6;285(32):24466-76. doi: 10.1074/jbc.M110.109801. Epub 2010, Jun 1. PMID:20516061 doi:http://dx.doi.org/10.1074/jbc.M110.109801
↑ Maynes JT, Perreault KR, Cherney MM, Luu HA, James MN, Holmes CF. Crystal structure and mutagenesis of a protein phosphatase-1:calcineurin hybrid elucidate the role of the beta12-beta13 loop in inhibitor binding. J Biol Chem. 2004 Oct 8;279(41):43198-206. Epub 2004 Jul 26. PMID:15280359 doi:10.1074/jbc.M407184200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1u32"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid==
-<StructureSection load='1u32' size='340' side='right' caption='[[1u32]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='1u32' size='340' side='right'caption='[[1u32]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1u32]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U32 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1u32]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U32 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1U32 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OKA:OKADAIC+ACID'>OKA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OKA:OKADAIC+ACID'>OKA</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP1CC ([http://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'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u32 OCA], [http://pdbe.org/1u32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u32 RCSB], [http://www.ebi.ac.uk/pdbsum/1u32 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u32 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1u32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u32 OCA], [http://pdbe.org/1u32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u32 RCSB], [http://www.ebi.ac.uk/pdbsum/1u32 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u32 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 30: / Line 30: @@
 </div>
 <div class="pdbe-citations 1u32" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Serine/threonine protein phosphatase|Serine/threonine protein phosphatase]]
 == References ==
 <references/>
@@ Line 38: / Line 35: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Phosphoprotein phosphatase]]
 [[Category: Cherney, M M]]

1u32

From Proteopedia

Revision as of 07:19, 30 December 2020

Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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