3hnf

Crystal structure of human ribonucleotide reductase 1 bound to the effectors TTP and dATP

spinqualitylabelsall models 3hnf, resolution 3.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3hnf 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 3.16Å Ligands: DTP, MG, SO4, TTP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RIR1_HUMAN Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Publication Abstract from PubMed Ribonucleotide reductase (RR) is an alpha(n)beta(n) (RR1-RR2) complex that maintains balanced dNTP pools by reducing NDPs to dNDPs. RR1 is the catalytic subunit, and RR2 houses the free radical required for catalysis. RR is allosterically regulated by its activator ATP and its inhibitor dATP, which regulate RR activity by inducing oligomerization of RR1. Here, we report the first X-ray structures of human RR1 bound to TTP alone, dATP alone, TTP-GDP, TTP-ATP, and TTP-dATP. These structures provide insights into regulation of RR by ATP or dATP. At physiological dATP concentrations, RR1 forms inactive hexamers. We determined the first X-ray structure of the RR1-dATP hexamer and used single-particle electron microscopy to visualize the alpha(6)-betabeta'-dATP holocomplex. Site-directed mutagenesis and functional assays confirm that hexamerization is a prerequisite for inhibition by dATP. Our data indicate a mechanism for regulating RR activity by dATP-induced oligomerization. Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization.,Fairman JW, Wijerathna SR, Ahmad MF, Xu H, Nakano R, Jha S, Prendergast J, Welin RM, Flodin S, Roos A, Nordlund P, Li Z, Walz T, Dealwis CG Nat Struct Mol Biol. 2011 Mar;18(3):316-22. Epub 2011 Feb 20. PMID:21336276 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribonucleotide reductase 3D structures

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