6U9O
Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Fully compressed filament segment reconstruction.
Summary for 6U9O
| Entry DOI | 10.2210/pdb6u9o/pdb |
| Related | 6U8E 6U8N 6U8R 6U8S |
| EMDB information | 20687 20688 20690 20691 20701 |
| Descriptor | Inosine-5'-monophosphate dehydrogenase 2, GUANOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | metabolism, filament, allostery, adenine, guanine, biosynthetic protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 16 |
| Total formula weight | 924209.38 |
| Authors | Johnson, M.C.,Kollman, J.M. (deposition date: 2019-09-09, release date: 2020-03-25, Last modification date: 2024-03-20) |
| Primary citation | Johnson, M.C.,Kollman, J.M. Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation. Elife, 9:-, 2020 Cited by PubMed Abstract: 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. PubMed: 31999252DOI: 10.7554/eLife.53243 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.36 Å) |
Structure validation
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