2bji

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[[Image:2bji.png|left|200px]]
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==HIGH RESOLUTION STRUCTURE OF MYO-INOSITOL MONOPHOSPHATASE, THE TARGET OF LITHIUM THERAPY==
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<StructureSection load='2bji' size='340' side='right' caption='[[2bji]], [[Resolution|resolution]] 1.24&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2bji]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BJI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BJI FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Inositol-phosphate_phosphatase Inositol-phosphate phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.25 3.1.3.25] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bji OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bji RCSB], [http://www.ebi.ac.uk/pdbsum/2bji PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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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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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bj/2bji_consurf.spt"</scriptWhenChecked>
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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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</jmolCheckbox>
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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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Inositol monophosphatase is a key enzyme of the phosphatidylinositol signalling pathway and the putative target of the mood-stabilizing drug lithium. The crystal structure of bovine inositol monophosphatase has been determined at 1.4 A resolution in complex with the physiological magnesium ion ligands. Three magnesium ions are octahedrally coordinated at the active site of each of the two subunits of the inositol monophosphatase dimer and a detailed three-metal mechanism is proposed. Ligands to the three metals include the side chains of Glu70, Asp90, Asp93 and Asp220, the backbone carbonyl group of Ile92 and several solvent molecules, including the proposed nucleophilic water molecule (W1) ligated by both Mg-1 and Mg-3. Modelling of the phosphate moiety of inositol monophosphate to superpose the axial phosphate O atoms onto three active-site water molecules orientates the phosphoester bond for in-line attack by the nucleophilic water which is activated by Thr95. Modelling of the pentacoordinate transition state suggests that the 6-OH group of the inositol moiety stabilizes the developing negative charge by hydrogen bonding to a phosphate O atom. Modelling of the post-reaction complex suggests a role for a second water molecule (W2) ligated by Mg-2 and Asp220 in protonating the departing inositolate. This second water molecule is absent in related structures in which lithium is bound at site 2, providing a rationale for enzyme inhibition by this simple monovalent cation. The higher resolution structural information on the active site of inositol monophosphatase will facilitate the design of substrate-based inhibitors and aid in the development of better therapeutic agents for bipolar disorder (manic depression).
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{{STRUCTURE_2bji| PDB=2bji | SCENE= }}
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High-resolution structure of myo-inositol monophosphatase, the putative target of lithium therapy.,Gill R, Mohammed F, Badyal R, Coates L, Erskine P, Thompson D, Cooper J, Gore M, Wood S Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):545-55. Epub 2005, Apr 20. PMID:15858264<ref>PMID:15858264</ref>
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===HIGH RESOLUTION STRUCTURE OF MYO-INOSITOL MONOPHOSPHATASE, THE TARGET OF LITHIUM THERAPY===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_15858264}}
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==About this Structure==
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[[2bji]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BJI OCA].
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==See Also==
==See Also==
*[[Inositol Monophosphatase|Inositol Monophosphatase]]
*[[Inositol Monophosphatase|Inositol Monophosphatase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015858264</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Inositol-phosphate phosphatase]]
[[Category: Inositol-phosphate phosphatase]]

Revision as of 03:15, 29 September 2014

HIGH RESOLUTION STRUCTURE OF MYO-INOSITOL MONOPHOSPHATASE, THE TARGET OF LITHIUM THERAPY

2bji, resolution 1.24Å

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