Ribonucleotide reductase class I with different radical generating clusters
Résumé
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