7rgd: Difference between revisions
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==HUMAN RETINAL VARIANT IMPDH1(595) TREATED WITH GTP, ATP, IMP, NAD+, OCTAMER-CENTERED== | ==HUMAN RETINAL VARIANT IMPDH1(595) TREATED WITH GTP, ATP, IMP, NAD+, OCTAMER-CENTERED== | ||
<StructureSection load='7rgd' size='340' side='right'caption='[[7rgd]]' scene=''> | <StructureSection load='7rgd' size='340' side='right'caption='[[7rgd]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RGD FirstGlance]. <br> | <table><tr><td colspan='2'>[[7rgd]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RGD FirstGlance]. <br> | ||
</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=7rgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rgd OCA], [https://pdbe.org/7rgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rgd RCSB], [https://www.ebi.ac.uk/pdbsum/7rgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rgd ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <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='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> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7rgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rgd OCA], [https://pdbe.org/7rgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rgd RCSB], [https://www.ebi.ac.uk/pdbsum/7rgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rgd 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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7rgd" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: IMP dehydrogenase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Burrell | [[Category: Burrell, A L]] | ||
[[Category: Kollman | [[Category: Kollman, J M]] | ||
[[Category: Adenine]] | |||
[[Category: Allostery]] | |||
[[Category: Filament]] | |||
[[Category: Metabolism]] | |||
[[Category: Oxidoreductase]] | |||
Revision as of 07:13, 27 January 2022
HUMAN RETINAL VARIANT IMPDH1(595) TREATED WITH GTP, ATP, IMP, NAD+, OCTAMER-CENTERED
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