6u8n
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human IMPDH2 treated with ATP, IMP, and NAD+. Fully extended filament segment reconstruction.== | |
| + | <StructureSection load='6u8n' size='340' side='right'caption='[[6u8n]], [[Resolution|resolution]] 3.29Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6u8n]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U8N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U8N FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6u8e|6u8e]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6u8n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8n OCA], [http://pdbe.org/6u8n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u8n RCSB], [http://www.ebi.ac.uk/pdbsum/6u8n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8n ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/IMDH2_HUMAN IMDH2_HUMAN]] 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. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.[HAMAP-Rule:MF_03156] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand. Self-assembly of metabolic enzymes is increasingly recognized as a general mechanism for regulating activity, typically by stabilizing specific conformations of an enzyme, but the regulatory role of IMPDH filaments has remained unclear. Here, we report a series of human IMPDH2 cryo-EM structures in both active and inactive conformations. The structures define the mechanism of filament assembly, and reveal how filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions that require expansion of guanine nucleotide pools. Tuning sensitivity to an allosteric inhibitor distinguishes IMPDH from other metabolic filaments, and highlights the diversity of regulatory outcomes that can emerge from self-assembly. | ||
| - | + | Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation.,Johnson MC, Kollman JM Elife. 2020 Jan 30;9. pii: 53243. doi: 10.7554/eLife.53243. PMID:31999252<ref>PMID:31999252</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6u8n" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: IMP dehydrogenase]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Johnson, M C]] | ||
| + | [[Category: Kollman, J M]] | ||
| + | [[Category: Adenine]] | ||
| + | [[Category: Allostery]] | ||
| + | [[Category: Biosynthetic protein]] | ||
| + | [[Category: Filament]] | ||
| + | [[Category: Guanine]] | ||
| + | [[Category: Metabolism]] | ||
Revision as of 10:21, 27 March 2020
Human IMPDH2 treated with ATP, IMP, and NAD+. Fully extended filament segment reconstruction.
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