Ribonucleotide reductase class I with different radical generating clusters

Ane B. Tomter (1) , Giorgio Zoppellaro (1) , Niels H. Andersen (1) , Hans-Petter Hersleth (1) , Marta Hammestad (1) , Asmund K. Rohr (1) , Guro K. Sandvik (1) , Kari R. Strand (1) , Goran E. Nilsson (1) , Caleb B. Bell (2) , Anne-Laure Barra (3) , Emmanuelle Blasco (4) , Laurent Le Pape (4) , Edward I. Solomon (2) , K. Kristoffer Andersson (1)

1 Department of Molecular Biosciences [Oslo]
2 Department of Chemistry [Stanford]
3 LNCMI-G - Laboratoire national des champs magnétiques intenses - Grenoble
4 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux

Ribonucleotide reductase (RNR) catalyzes the rate limiting step in DNA synthesis where ribonucleotides are reduced to their corresponding deoxyribonucleotides. They are formed through a radical-induced reduction of ribonucleotides. Three classes of RNR generate the catalytically active site thiyl radical using different co-factors: a tyrosyl-radical in most cases (class I), homolytic cleavage of deoxyadenosyl-cobalamin (class II), or a glycyl-radical (class III), respectively. Class I RNR has a larger subunit R1/R1E containing the active site and a smaller subunit R2/R2F with (the thiyl-generating power from) a tyrosyl radical or an oxidized iron-manganese cluster and is reviewed herein. Class I is divided into subclasses, Ia (tyrosyl-radical and di-iron-oxygen cluster), Ib (tyrosyl-radical and di-manganese-oxygen cluster) and Ic (an iron-manganese cluster). Presented here is an overview of recent developments in the understanding of class I RNR: metal-ion cluster identities, novel 3D structures, magnetic-optical properties, and reaction mechanisms. It became clear in the last years that the primitive bacterial RNR sources can utilize different metal-ion clusters to fulfil function. Within class Ia that includes members from eukaryotes (mammalians, fish) and some viruses species, the presence of hydrogen bonding interactions from water at different distances with the tyrosyl-radical site can occur. This demonstrates a large versatility in the mechanism to form the thiyl radical.

Mots clés: Ribonucleotide reductase; R2 subunit; Di-iron metal cluster; Di-manganese metal cluster; Electron paramagnetic resonance (EPR); Resonance Raman (rRaman); Circular dichroism/magnetic circular dichroism (CD/MCD); Density functional theory (DFT); SQUID magnetic measurement; MAGNETIC CIRCULAR-DICHROISM; HERPES-SIMPLEX-VIRUS; TYROSYL RADICAL-DIIRON(III) COFACTOR; METHANE MONOOXYGENASE HYDROXYLASE; HIGH-FIELD EPR; ELECTRONIC-STRUCTURE DESCRIPTION; DINUCLEAR MANGANESE(II) COMPLEX; METHYLOCOCCUS-CAPSULATUS BATH; SITE-DIRECTED MUTAGENESIS; NONHEME IRON ENZYMES

Domaines: Catalyse; Chimie inorganique; Biochimie, Biologie Moléculaire; Biophysique

Ane B. Tomter, Giorgio Zoppellaro, Niels H. Andersen, Hans-Petter Hersleth, Marta Hammestad, et al.. Ribonucleotide reductase class I with different radical generating clusters. Coordination Chemistry Reviews, 2013, 257 (1), pp.3-26. ⟨10.1016/j.ccr.2012.05.021⟩. ⟨hal-01239000⟩