4z87: Difference between revisions
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==Structure of the IMP dehydrogenase from Ashbya gossypii bound to GDP== | ==Structure of the IMP dehydrogenase from Ashbya gossypii bound to GDP== | ||
<StructureSection load='4z87' size='340' side='right' caption='[[4z87]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='4z87' size='340' side='right'caption='[[4z87]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4z87]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z87 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4z87]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Eremothecium_gossypii_ATCC_10895 Eremothecium gossypii ATCC 10895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z87 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z87 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4z87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z87 OCA], [https://pdbe.org/4z87 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z87 RCSB], [https://www.ebi.ac.uk/pdbsum/4z87 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z87 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/Q756Z6_ASHGO Q756Z6_ASHGO] 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.[HAMAP-Rule:MF_03156] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4z87" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4z87" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Eremothecium gossypii ATCC 10895]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Buey RM]] | ||
[[Category: Revuelta | [[Category: Revuelta JL]] | ||
[[Category: | [[Category: De Pereda JM]] | ||
Latest revision as of 13:58, 10 January 2024
Structure of the IMP dehydrogenase from Ashbya gossypii bound to GDPStructure of the IMP dehydrogenase from Ashbya gossypii bound to GDP
Structural highlights
FunctionQ756Z6_ASHGO 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.[HAMAP-Rule:MF_03156] Publication Abstract from PubMedInosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches. Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases.,Buey RM, Ledesma-Amaro R, Velazquez-Campoy A, Balsera M, Chagoyen M, de Pereda JM, Revuelta JL Nat Commun. 2015 Nov 12;6:8923. doi: 10.1038/ncomms9923. PMID:26558346[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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