6I0O
Structure of human IMP dehydrogenase, isoform 2, bound to GTP
Summary for 6I0O
| Entry DOI | 10.2210/pdb6i0o/pdb |
| Related | 6I0M |
| Descriptor | Inosine-5'-monophosphate dehydrogenase 2, GUANOSINE-5'-TRIPHOSPHATE, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, de novo guanine nucleotide biosynthesis, biosynthetic protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 117950.99 |
| Authors | Buey, R.M.,Fernandez-Justel, D.,Revuelta, J.L. (deposition date: 2018-10-26, release date: 2019-01-30, Last modification date: 2024-01-24) |
| Primary citation | Fernandez-Justel, D.,Nunez, R.,Martin-Benito, J.,Jimeno, D.,Gonzalez-Lopez, A.,Soriano, E.M.,Revuelta, J.L.,Buey, R.M. A Nucleotide-Dependent Conformational Switch Controls the Polymerization of Human IMP Dehydrogenases to Modulate their Catalytic Activity. J. Mol. Biol., 431:956-969, 2019 Cited by PubMed Abstract: Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo GTP biosynthetic pathway and plays essential roles in cell proliferation. As a clinical target, IMPDH has been studied for decades, but it has only been within the last years that we are starting to understand the complexity of the mechanisms of its physiological regulation. Here, we report structural and functional insights into how adenine and guanine nucleotides control a conformational switch that modulates the assembly of the two human IMPDH enzymes into cytoophidia and allosterically regulates their catalytic activity. In vitro reconstituted micron-length cytoophidia-like structures show catalytic activity comparable to unassembled IMPDH but, in turn, are more resistant to GTP/GDP allosteric inhibition. Therefore, IMPDH cytoophidia formation facilitates the accumulation of high levels of guanine nucleotides when the cell requires it. Finally, we demonstrate that most of the IMPDH retinopathy-associated mutations abrogate GTP/GDP-induced allosteric inhibition and alter cytoophidia dynamics. PubMed: 30664871DOI: 10.1016/j.jmb.2019.01.020 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.623 Å) |
Structure validation
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