7rfi
From Proteopedia
(Difference between revisions)
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<StructureSection load='7rfi' size='340' side='right'caption='[[7rfi]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='7rfi' size='340' side='right'caption='[[7rfi]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=7rfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfi OCA], [https://pdbe.org/7rfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfi RCSB], [https://www.ebi.ac.uk/pdbsum/7rfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfi 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=7rfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfi OCA], [https://pdbe.org/7rfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfi RCSB], [https://www.ebi.ac.uk/pdbsum/7rfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfi ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 7rfi" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: IMP dehydrogenase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Burrell | + | [[Category: Burrell AL]] |
| - | [[Category: Kollman | + | [[Category: Kollman JM]] |
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Current revision
HUMAN RETINAL VARIANT IMPDH1(595) TREATED WITH GTP, ATP, IMP, NAD+, INTERFACE-CENTERED
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