1jp4
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1jp4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jp4, resolution 1.69Å" /> '''Crystal Structure of...)
Next diff →
Revision as of 16:19, 20 November 2007
|
Crystal Structure of an Enzyme Displaying both Inositol-Polyphosphate 1-Phosphatase and 3'-Phosphoadenosine-5'-Phosphate Phosphatase Activities
Overview
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.
About this Structure
1JP4 is a Single protein structure of sequence from Rattus norvegicus with PO4, MG, AMP and BME as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Nov 20 18:26:32 2007
