2bji: Difference between revisions
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[[Image:2bji.gif|left|200px]]<br /> | [[Image:2bji.gif|left|200px]]<br /><applet load="2bji" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2bji" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="2bji, resolution 1.24Å" /> | caption="2bji, resolution 1.24Å" /> | ||
'''HIGH RESOLUTION STRUCTURE OF MYO-INOSITOL MONOPHOSPHATASE, THE TARGET OF LITHIUM THERAPY'''<br /> | '''HIGH RESOLUTION STRUCTURE OF MYO-INOSITOL MONOPHOSPHATASE, THE TARGET OF LITHIUM THERAPY'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2BJI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] | 2BJI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Mg Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BJI OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
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Revision as of 19:39, 18 December 2007
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HIGH RESOLUTION STRUCTURE OF MYO-INOSITOL MONOPHOSPHATASE, THE TARGET OF LITHIUM THERAPY
OverviewOverview
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).
About this StructureAbout this Structure
2BJI is a Single protein structure of sequence from Bos taurus with MG as ligand. Active as Inositol-phosphate phosphatase, with EC number 3.1.3.25 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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
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