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[[Image:1ak5.gif|left|200px]]<br /><applet load="1ak5" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1ak5, resolution 2.3&Aring;" />
'''INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH) FROM TRITRICHOMONAS FOETUS'''<br />


==Overview==
==INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH) FROM TRITRICHOMONAS FOETUS==
Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for the control of parasitic infections. The enzyme catalyzes the oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed step in de novo guanosine monophosphate (GMP) biosynthesis. We have determined the crystal structures of IMPDH from the protozoan parasite Tritrichomonas foetus in the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A resolution. Each monomer of this tetrameric enzyme is comprised of two domains, the largest of which includes an eight-stranded parallel beta/alpha-barrel that contains the enzyme active site at the C termini of the barrel beta-strands. A second domain, comprised of residues 102-220, is disordered in the crystal. IMPDH is expected to be active as a tetramer, since the active site cavity is formed by strands from adjacent subunits. An intrasubunit disulfide bond, seen in the crystal structure, may stabilize the protein in a less active form, as high concentrations of reducing agent have been shown to increase enzyme activity. Disorder at the active site suggests that a high degree of flexibility may be inherent in the catalytic function of IMPDH. Unlike IMPDH from other species, the T. foetus enzyme has a single arginine that is largely responsible for coordinating the substrate phosphate in the active site. This structural uniqueness may facilitate structure-based identification and design of compounds that specifically inhibit the parasite enzyme.
<StructureSection load='1ak5' size='340' side='right'caption='[[1ak5]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ak5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tritrichomonas_suis Tritrichomonas suis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AK5 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=1ak5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ak5 OCA], [https://pdbe.org/1ak5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ak5 RCSB], [https://www.ebi.ac.uk/pdbsum/1ak5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ak5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IMDH_TRIFO IMDH_TRIFO] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism.<ref>PMID:10029522</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/ak/1ak5_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=1ak5 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1AK5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tritrichomonas_foetus Tritrichomonas foetus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AK5 OCA].
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]]
 
== References ==
==Reference==
<references/>
Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex., Whitby FG, Luecke H, Kuhn P, Somoza JR, Huete-Perez JA, Phillips JD, Hill CP, Fletterick RJ, Wang CC, Biochemistry. 1997 Sep 2;36(35):10666-74. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9271497 9271497]
__TOC__
[[Category: IMP dehydrogenase]]
</StructureSection>
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Tritrichomonas foetus]]
[[Category: Tritrichomonas suis]]
[[Category: Whitby, F G.]]
[[Category: Whitby FG]]
[[Category: SO4]]
[[Category: alpha-8-beta-8 barrel]]
[[Category: c4-tetramer]]
[[Category: dehydrogenase]]
[[Category: oxidoreductase]]
[[Category: purine metabolism]]
[[Category: tetramer]]
[[Category: tim barrel]]
 
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