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| | <StructureSection load='4z0g' size='340' side='right'caption='[[4z0g]], [[Resolution|resolution]] 1.25Å' scene=''> | | <StructureSection load='4z0g' size='340' side='right'caption='[[4z0g]], [[Resolution|resolution]] 1.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4z0g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ashgo Ashgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z0G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4z0g]] is a 2 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=4Z0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z0G 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | + | </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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xwu|4xwu]]</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=4z0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z0g OCA], [https://pdbe.org/4z0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z0g RCSB], [https://www.ebi.ac.uk/pdbsum/4z0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z0g ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGOS_AER117W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284811 ASHGO])</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=4z0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z0g OCA], [http://pdbe.org/4z0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z0g RCSB], [http://www.ebi.ac.uk/pdbsum/4z0g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z0g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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] | + | [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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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Inosine monophosphate dehydrogenase|Inosine monophosphate dehydrogenase]] | + | *[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ashgo]] | + | [[Category: Eremothecium gossypii ATCC 10895]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Buey, R M]] | + | [[Category: Buey RM]] |
| - | [[Category: Pereda, J M.de]]
| + | [[Category: Revuelta JL]] |
| - | [[Category: Revuelta, J L]] | + | [[Category: De Pereda JM]] |
| - | [[Category: Oxidoreductase]] | + | |
| Structural highlights
Function
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]
Publication Abstract from PubMed
Inosine-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 Also
References
- ↑ Buey RM, Ledesma-Amaro R, Velazquez-Campoy A, Balsera M, Chagoyen M, de Pereda JM, Revuelta JL. Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases. Nat Commun. 2015 Nov 12;6:8923. doi: 10.1038/ncomms9923. PMID:26558346 doi:http://dx.doi.org/10.1038/ncomms9923
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