6AUI
Human ribonucleotide reductase large subunit (alpha) with dATP and CDP
Summary for 6AUI
| Entry DOI | 10.2210/pdb6aui/pdb |
| EMDB information | 7006 |
| Descriptor | Ribonucleoside-diphosphate reductase large subunit, 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | ribonucleotide reductase electron transfer radical chemistry thiyl radical, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 6 |
| Total formula weight | 562707.25 |
| Authors | Brignole, E.J.,Drennan, C.L.,Asturias, F.J.,Tsai, K.L.,Penczek, P.A. (deposition date: 2017-09-01, release date: 2018-04-18, Last modification date: 2024-03-13) |
| Primary citation | Brignole, E.J.,Tsai, K.L.,Chittuluru, J.,Li, H.,Aye, Y.,Penczek, P.A.,Stubbe, J.,Drennan, C.L.,Asturias, F. 3.3- angstrom resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound. Elife, 7:-, 2018 Cited by PubMed Abstract: Ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by cryo-electron microscopy (EM) of a dATP-inhibited state of human RNR. This structure, which was determined in the presence of substrate CDP and allosteric regulators ATP and dATP, has three α units arranged in an α ring. At near-atomic resolution, these data provide insight into the molecular basis for CDP recognition by allosteric specificity effectors dATP/ATP. Additionally, we present lower-resolution EM structures of human α in the presence of both the anticancer drug clofarabine triphosphate and β. Together, these structures support a model for RNR inhibition in which β is excluded from binding in a radical transfer competent position when α exists as a stable hexamer. PubMed: 29460780DOI: 10.7554/eLife.31502 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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