1jp4

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[[Image:1jp4.jpg|left|200px]]
 
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{{Structure
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==Crystal Structure of an Enzyme Displaying both Inositol-Polyphosphate 1-Phosphatase and 3'-Phosphoadenosine-5'-Phosphate Phosphatase Activities==
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|PDB= 1jp4 |SIZE=350|CAPTION= <scene name='initialview01'>1jp4</scene>, resolution 1.69&Aring;
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<StructureSection load='1jp4' size='340' side='right'caption='[[1jp4]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
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<table><tr><td colspan='2'>[[1jp4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JP4 FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69&#8491;</td></tr>
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|GENE= Sal3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jp4 OCA], [https://pdbe.org/1jp4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jp4 RCSB], [https://www.ebi.ac.uk/pdbsum/1jp4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jp4 ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jp4 OCA], [http://www.ebi.ac.uk/pdbsum/1jp4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jp4 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/BPNT1_RAT BPNT1_RAT] Converts adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to adenosine 5'-phosphosulfate (APS) and 3'(2')-phosphoadenosine 5'- phosphate (PAP) to AMP. Has 1000-fold lower activity towards inositol 1,4-bisphosphate (Ins(1,4)P2) and inositol 1,3,4-trisphosphate (Ins(1,3,4)P3), but does not hydrolyze Ins(1)P, Ins(3,4)P2, Ins(1,3,4,5)P4 or InsP6.<ref>PMID:10347153</ref>
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== Evolutionary Conservation ==
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'''Crystal Structure of an Enzyme Displaying both Inositol-Polyphosphate 1-Phosphatase and 3'-Phosphoadenosine-5'-Phosphate Phosphatase Activities'''
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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==Overview==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jp/1jp4_consurf.spt"</scriptWhenChecked>
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Lithium cations exert profound and selective psychopharmacological effects on ameliorate manic-depressive psychosis. Although lithium is an effective drug for both treatment and prophylaxis of bipolar disorder, the precise mechanism of action is not well understood. Lithium acts as both an uncompetitive and non-competitive inhibitor of several lithium- sensitive phosphatases with regard to substrate and magnesium cofactor, respectively. In this work, we report the crystal structure and reaction mechanism of Rattus norvegicus 3'-phosphoadenosine 5'-phosphate and inositol 1,4-bisphosphate phosphatase (RnPIP), a recently identified target of lithium therapy. This Li(+)-sensitive enzyme plays a crucial role in several cellular processes, such as RNA processing, sulphation reactions and probably inositol recycling. RnPIP specifically removes the 3'-phosphate group of 3'-phosphoadenosine 5'-phosphate (PAP) and the 1'-phosphate group of inositol 1,4-bisphosphate (I(1),(4)P(2)) producing AMP and inositol 4'-phosphate, respectively. The crystal structure of RnPIP complexed with AMP, Pi and magnesium ions at 1.69 A resolution provides insight into the reaction mechanism of the hydrolysis of PAP. The core fold of the enzyme is equivalent to that found in other Li(+)-sensitive phosphatases, such as inositol monophosphatase, but molecular modelling of I(1),(4)P(2) in the RnPIP active site reveals important structural determinants that accommodate this additional substrate. RnPIP is potently inhibited by lithium and, as the accumulation of PAP inhibits a variety of proteins, including sulphotransferases and RNA processing enzymes, this dual specificity enzyme represents a potential target of lithium action, in addition to inositol monophosphatases.
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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==About this Structure==
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</jmolCheckbox>
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1JP4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JP4 OCA].
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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=1jp4 ConSurf].
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<div style="clear:both"></div>
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==Reference==
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== References ==
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Crystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3'-phosphoadenosine-5'-phosphate phosphatase activities: a novel target of lithium therapy., Patel S, Yenush L, Rodriguez PL, Serrano R, Blundell TL, J Mol Biol. 2002 Jan 25;315(4):677-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11812139 11812139]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Blundell TL]]
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[[Category: Blundell, T L.]]
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[[Category: Patel S]]
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[[Category: Patel, S.]]
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[[Category: Rodriguez PL]]
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[[Category: Rodriguez, P L.]]
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[[Category: Serrano R]]
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[[Category: Serrano, R.]]
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[[Category: Yenush L]]
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[[Category: Yenush, L.]]
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[[Category: protein-product complex]]
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[[Category: sugar nucleotidase fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:36:50 2008''
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Current revision

Crystal Structure of an Enzyme Displaying both Inositol-Polyphosphate 1-Phosphatase and 3'-Phosphoadenosine-5'-Phosphate Phosphatase Activities

PDB ID 1jp4

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