6R4T
Crystal structure of the Pri1 subunit of human primase bound to vidarabine triphosphate
Summary for 6R4T
| Entry DOI | 10.2210/pdb6r4t/pdb |
| Related | 6R4S 6R4U 6R5D 6R5E 6RB4 |
| Descriptor | DNA primase small subunit, ZINC ION, MANGANESE (II) ION, ... (6 entities in total) |
| Functional Keywords | primase, dna-dependent rna polymerase, atp, priming, replication |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 98820.22 |
| Authors | Kilkenny, M.L.,Pellegrini, L. (deposition date: 2019-03-24, release date: 2019-09-11, Last modification date: 2024-01-24) |
| Primary citation | Holzer, S.,Rzechorzek, N.J.,Short, I.R.,Jenkyn-Bedford, M.,Pellegrini, L.,Kilkenny, M.L. Structural Basis for Inhibition of Human Primase by Arabinofuranosyl Nucleoside Analogues Fludarabine and Vidarabine. Acs Chem.Biol., 14:1904-1912, 2019 Cited by PubMed Abstract: Nucleoside analogues are widely used in clinical practice as chemotherapy drugs. Arabinose nucleoside derivatives such as fludarabine are effective in the treatment of patients with acute and chronic leukemias and non-Hodgkin's lymphomas. Although nucleoside analogues are generally known to function by inhibiting DNA synthesis in rapidly proliferating cells, the identity of their targets and mechanism of action are often not known in molecular detail. Here we provide a structural basis for arabinose nucleotide-mediated inhibition of human primase, the DNA-dependent RNA polymerase responsible for initiation of DNA synthesis in DNA replication. Our data suggest ways in which the chemical structure of fludarabine could be modified to improve its specificity and affinity toward primase, possibly leading to less toxic and more effective therapeutic agents. PubMed: 31479243DOI: 10.1021/acschembio.9b00367 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.35 Å) |
Structure validation
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