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1jp4

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Revision as of 09:16, 17 January 2018

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

Structural highlights

1jp4 is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	Sal3 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

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

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.

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:11812139^[2]

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

References

↑ Lopez-Coronado JM, Belles JM, Lesage F, Serrano R, Rodriguez PL. A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. J Biol Chem. 1999 Jun 4;274(23):16034-9. PMID:10347153
↑ Patel S, Yenush L, Rodriguez PL, Serrano R, Blundell TL. Crystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3'-phosphoadenosine-5'-phosphate phosphatase activities: a novel target of lithium therapy. J Mol Biol. 2002 Jan 25;315(4):677-85. PMID:11812139 doi:http://dx.doi.org/10.1006/jmbi.2001.5271

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/1jp4"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of an Enzyme Displaying both Inositol-Polyphosphate 1-Phosphatase and 3'-Phosphoadenosine-5'-Phosphate Phosphatase Activities==
 <StructureSection load='1jp4' size='340' side='right' caption='[[1jp4]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sal3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=1jp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jp4 OCA], [http://pdbe.org/1jp4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jp4 RCSB], [http://www.ebi.ac.uk/pdbsum/1jp4 PDBsum]</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=1jp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jp4 OCA], [http://pdbe.org/1jp4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jp4 RCSB], [http://www.ebi.ac.uk/pdbsum/1jp4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jp4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jp/1jp4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jp/1jp4_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1jp4

From Proteopedia

Revision as of 09:16, 17 January 2018

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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