3PAW

Low resolution X-ray crystal structure of Yeast Rnr1p with dATP bound in the A-site

Summary for 3PAW

• Entry DOI: 10.2210/pdb3paw/pdb
• Descriptor: Ribonucleoside-diphosphate reductase large chain 1 (1 entity in total)
• Functional Keywords: ribonucleotide reductase, oxidoreductase, nucleotide binding
• Biological source: Saccharomyces cerevisiae (yeast)
• Cellular location: Cytoplasm: P21524
• Total number of polymer chains: 4
• Total formula weight: 398691.94

Authors

Fairman, J.W.,Wijerathna, S.R.,Dealwis, C.G. (deposition date: 2010-10-19, release date: 2011-02-23, Last modification date: 2024-02-21)

Primary citation

Fairman, J.W.,Wijerathna, S.R.,Ahmad, M.F.,Xu, H.,Nakano, R.,Jha, S.,Prendergast, J.,Welin, R.M.,Flodin, S.,Roos, A.,Nordlund, P.,Li, Z.,Walz, T.,Dealwis, C.G.
Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization.
Nat.Struct.Mol.Biol., 18:316-322, 2011

PubMed Abstract: Ribonucleotide reductase (RR) is an α(n)β(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 α(6)-ββ'-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.

PubMed: 21336276
DOI: 10.1038/nsmb.2007

Experimental method

X-RAY DIFFRACTION (6.61 Å)