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| <StructureSection load='7rff' size='340' side='right'caption='[[7rff]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='7rff' size='340' side='right'caption='[[7rff]], [[Resolution|resolution]] 2.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7rff]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFF FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFF FirstGlance]. <br> |
| </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] </span></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7Å</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=7rff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rff OCA], [https://pdbe.org/7rff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rff RCSB], [https://www.ebi.ac.uk/pdbsum/7rff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rff ProSAT]</span></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=7rff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rff OCA], [https://pdbe.org/7rff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rff RCSB], [https://www.ebi.ac.uk/pdbsum/7rff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rff ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Inosine-5'-monophosphate dehydrogenase (IMPDH), a key regulatory enzyme in purine nucleotide biosynthesis, dynamically assembles filaments in response to changes in metabolic demand. Humans have two isoforms: IMPDH2 filaments reduce sensitivity to feedback inhibition, while IMPDH1 assembly remains uncharacterized. IMPDH1 plays a unique role in retinal metabolism, and point mutants cause blindness. Here, in a series of cryogenic-electron microscopy structures we show that human IMPDH1 assembles polymorphic filaments with different assembly interfaces in extended and compressed states. Retina-specific splice variants introduce structural elements that reduce sensitivity to GTP inhibition, including stabilization of the extended filament form. Finally, we show that IMPDH1 disease mutations fall into two classes: one disrupts GTP regulation and the other has no effect on GTP regulation or filament assembly. These findings provide a foundation for understanding the role of IMPDH1 in retinal function and disease and demonstrate the diverse mechanisms by which metabolic enzyme filaments are allosterically regulated.
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| IMPDH1 retinal variants control filament architecture to tune allosteric regulation.,Burrell AL, Nie C, Said M, Simonet JC, Fernandez-Justel D, Johnson MC, Quispe J, Buey RM, Peterson JR, Kollman JM Nat Struct Mol Biol. 2022 Jan;29(1):47-58. doi: 10.1038/s41594-021-00706-2. Epub , 2022 Jan 10. PMID:35013599<ref>PMID:35013599</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7rff" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: IMP dehydrogenase]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Burrell, A L]] | | [[Category: Burrell AL]] |
| [[Category: Kollman, J M]] | | [[Category: Kollman JM]] |
| [[Category: Adenine]]
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| [[Category: Allostery]]
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| [[Category: Filament]]
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| [[Category: Metabolism]]
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| [[Category: Oxidoreductase]]
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