6r4u

Crystal structure of the Pri1 subunit of human primase bound to fludarabine triphosphate

spinqualitylabelsall models 6r4u, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6r4u is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: EDO, HFD, MN, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PRI1_HUMAN DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. Publication Abstract from PubMed 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 in vivo 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. Structural Basis for Inhibition of Human Primase by Arabinofuranosyl Nucleoside Analogues Fludarabine and Vidarabine.,Holzer S, Rzechorzek NJ, Short IR, Jenkyn-Bedford M, Pellegrini L, Kilkenny ML ACS Chem Biol. 2019 Sep 20;14(9):1904-1912. doi: 10.1021/acschembio.9b00367. Epub , 2019 Sep 11. PMID:31479243 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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