2hhm: Difference between revisions

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New page: left|200px<br /> <applet load="2hhm" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hhm, resolution 2.1Å" /> '''STRUCTURE OF INOSITO...
 
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[[Image:2hhm.gif|left|200px]]<br />
<applet load="2hhm" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2hhm, resolution 2.1&Aring;" />
'''STRUCTURE OF INOSITOL MONOPHOSPHATASE, THE PUTATIVE TARGET OF LITHIUM THERAPY'''<br />


==Overview==
==STRUCTURE OF INOSITOL MONOPHOSPHATASE, THE PUTATIVE TARGET OF LITHIUM THERAPY==
Inositol monophosphatase (EC 3.1.3.25), the putative molecular site of, action of lithium therapy for manic-depressive illness, plays a key role, in the phosphatidylinositol signaling pathway by catalyzing the hydrolysis, of inositol monophosphates. To provide a structural basis from which to, design better therapeutic agents for manic-depressive illness, the, structure of human inositol monophosphatase has been determined to 2.1-A, resolution by using x-ray crystallography. The enzyme exists as a dimer of, identical subunits, each folded into a five-layered sandwich of three, pairs of alpha-helices and two beta-sheets. Sulfate and an inhibitory, lanthanide cation (Gd3+) are bound at identical sites on each subunit and, establish the positions of the active sites. Each site is located in a, large hydrophilic cavern that is at the base of the two central helices, where several segments of secondary structure intersect. Comparison of the, phosphatase aligned sequences of several diverse genes with the, phosphatase structure suggests that the products of these genes and the, phosphatase form a structural family with a conserved metal binding site.
<StructureSection load='2hhm' size='340' side='right'caption='[[2hhm]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hhm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HHM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hhm OCA], [https://pdbe.org/2hhm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hhm RCSB], [https://www.ebi.ac.uk/pdbsum/2hhm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hhm ProSAT]</span></td></tr>
</table>
== Function ==
[https://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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/2hhm_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2hhm ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2HHM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and GD as [http://en.wikipedia.org/wiki/ligands ligands]. 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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HHM OCA].
*[[Inositol monophosphatase 3D structures|Inositol monophosphatase 3D structures]]
 
== References ==
==Reference==
<references/>
Structure of inositol monophosphatase, the putative target of lithium therapy., Bone R, Springer JP, Atack JR, Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10031-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=1332026 1332026]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Inositol-phosphate phosphatase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Bone R]]
[[Category: Bone, R.]]
[[Category: GD]]
[[Category: SO4]]
[[Category: hydrolase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:32:48 2007''

Latest revision as of 12:32, 14 February 2024

STRUCTURE OF INOSITOL MONOPHOSPHATASE, THE PUTATIVE TARGET OF LITHIUM THERAPYSTRUCTURE OF INOSITOL MONOPHOSPHATASE, THE PUTATIVE TARGET OF LITHIUM THERAPY

Structural highlights

2hhm is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T. Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1. J Biol Chem. 2007 Jan 5;282(1):637-46. Epub 2006 Oct 26. PMID:17068342 doi:http://dx.doi.org/10.1074/jbc.M604474200

2hhm, resolution 2.10Å

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