2bji

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{{Seed}}
 
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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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The line below this paragraph, containing "STRUCTURE_2bji", creates the "Structure Box" on the page.
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<StructureSection load='2bji' size='340' side='right'caption='[[2bji]], [[Resolution|resolution]] 1.24&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2bji]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2BJI FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.24&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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{{STRUCTURE_2bji| PDB=2bji | SCENE= }}
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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=2bji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bji OCA], [https://pdbe.org/2bji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bji RCSB], [https://www.ebi.ac.uk/pdbsum/2bji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bji ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IMPA1_BOVIN IMPA1_BOVIN] Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Has broad substrate specificity and can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates (By similarity). Is equally active with myo-inositol monophosphate and D-galactose 1-phosphate.[UniProtKB:P29218]<ref>PMID:9462881</ref>
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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/main_output.php?pdb_ID=2bji 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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===HIGH RESOLUTION STRUCTURE OF MYO-INOSITOL MONOPHOSPHATASE, THE TARGET OF LITHIUM THERAPY===
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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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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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<div class="pdbe-citations 2bji" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15858264}}, adds the Publication Abstract to the page
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*[[Inositol monophosphatase 3D structures|Inositol monophosphatase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15858264 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15858264}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2BJI is a [[Single protein]] structure of 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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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15858264 15858264]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Inositol-phosphate phosphatase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Badyal R]]
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[[Category: Badyal, R.]]
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[[Category: Coates L]]
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[[Category: Coates, L.]]
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[[Category: Cooper J]]
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[[Category: Cooper, J.]]
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[[Category: Erskine P]]
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[[Category: Erskine, P.]]
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[[Category: Gill R]]
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[[Category: Gill, R.]]
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[[Category: Gore M]]
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[[Category: Gore, M.]]
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[[Category: Mohammed F]]
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[[Category: Mohammed, F.]]
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[[Category: Thompson D]]
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[[Category: Thompson, D.]]
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[[Category: Wood S]]
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[[Category: Wood, S.]]
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[[Category: Aspartic proteinase mechanism]]
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[[Category: Aspartyl protease]]
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[[Category: Hydrolase]]
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[[Category: Succinimide]]
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[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:34:37 2008''
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Current revision

High Resolution Structure of myo-Inositol Monophosphatase, The Target of Lithium Therapy

PDB ID 2bji

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