View source for 6gj0


==Human IMPase with Mn==
<StructureSection load='6gj0' size='340' side='right' caption='[[6gj0]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gj0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GJ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJ0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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=6gj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gj0 OCA], [http://pdbe.org/6gj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gj0 RCSB], [http://www.ebi.ac.uk/pdbsum/6gj0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gj0 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/IMPA1_HUMAN IMPA1_HUMAN]] 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. 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.<ref>PMID:17068342</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lithium, which is still the gold standard in the treatment of bipolar disorder, has been proposed to inhibit inositol monophosphatase (IMPase) and is hypothesized to exert its therapeutic effects by attenuating phosphatidylinositol (PI) cell signalling. Drug-discovery efforts have focused on small-molecule lithium mimetics that would specifically inhibit IMPase without exhibiting the undesired side effects of lithium. L-690,330 is a potent bisphosphonate substrate-based inhibitor developed by Merck Sharp &amp; Dohme. To aid future structure-based inhibitor design, determination of the exact binding mechanism of L-690,330 to IMPase was of interest. Here, the high-resolution X-ray structure of human IMPase in complex with L690,330 and manganese ions determined at 1.39 A resolution is reported.

Co-crystallization of human inositol monophosphatase with the lithium mimetic L-690,330.,Kraft L, Roe SM, Gill R, Atack JR Acta Crystallogr D Struct Biol. 2018 Oct 1;74(Pt 10):973-978. doi:, 10.1107/S2059798318010380. Epub 2018 Oct 2. PMID:30289407<ref>PMID:30289407</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gj0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Kraft, L V]]
[[Category: Roe, S M]]
[[Category: Complex]]
[[Category: Hydrolase]]
[[Category: Impase]]
[[Category: Lithium]]