View source for 6uaj


==Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction.==
<StructureSection load='6uaj' size='340' side='right'caption='[[6uaj]], [[Resolution|resolution]] 3.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uaj]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UAJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UAJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.84&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6uaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uaj OCA], [https://pdbe.org/6uaj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uaj RCSB], [https://www.ebi.ac.uk/pdbsum/6uaj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uaj ProSAT]</span></td></tr>
</table>
== Function ==
[https://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]
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6uaj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Johnson MC]]
[[Category: Kollman JM]]