Amazing Diversity in Biochemical Roles of Fe(II)/2-Oxoglutarate Oxygenases

Abstract

Since their discovery in the 1960s, the family of Fe(II)/2-oxoglutarate-dependent oxygenases has undergone a tremendous expansion to include enzymes catalyzing a vast diversity of biologically important reactions. Recent examples highlight roles in controlling chromatin modification, transcription, mRNA demethylation, and mRNA splicing. Others generate modifications in tRNA, translation factors, ribosomes, and other proteins. Thus, oxygenases affect all components of molecular biology's central dogma, in which information flows from DNA to RNA to proteins. These enzymes also function in biosynthesis and catabolism of cellular metabolites, including antibiotics and signaling molecules. Due to their critical importance, ongoing efforts have targeted family members for the development of specific therapeutics. This review provides a general overview of recently characterized oxygenase reactions and their key biological roles.

Strongly Coupled Redox-Linked Conformational Switching at the Active Site of the Non-Heme Iron-Dependent Dioxygenase, TauD

“…The application of a semi-empirical model of heterogeneous thin layer electrochemistry showed that both models can yield comparable NPSV results using specific Fe-TauD potentials at the given mediator concentrations. However, no single ½ consistent with experimental observations across all the conditions tested here, giving strong support for intrinsic redox-linked reorganization in Fe-TauD, as follows.The largest hysteresis predicted for model[1] was 213 mV ( ½ TauD E = 0.0 mV), which is 85 mV smaller than that experimentally observed in 2OG-Fe-TauD and taurine-2OG-Fe-TauD and 128 mV smaller than that observed in Fe-TauD(Table S1). The magnitude of the hysteresis and apparent ½TauD E values in 2OG-Fe-TauD and taurine-2OG-Fe-TauD could be reproduced by model [2] using ½ A E = -130 mV and ½ A E  = 180 mV (Fig.…”

“…Calculated oxidation and reduction potentials of profiles generated using model[1]. Phases representing >50% of the observed oxidation or reduction are bolded.…”

Closely related viruses of the marine picoeukaryotic alga Ostreococcus lucimarinus exhibit different ecological strategies

“…However, there were aspects of the unique gene sets worth noting. OlV7 generally showed enrichment of functions involved in gene expression, such as expansion of the Fe(II)/2‐oxoglutarate‐dependent oxygenase protein family, which encompasses diverse functions affecting multiple steps in transcriptional and translational processes, as well as biosynthesis and degradation of cellular metabolites (Herr and Hausinger, ). Several cyanophage genomes also encode multiple copies of 2OG‐Fe(II) oxygenase superfamily proteins, presumed to function in DNA repair (Weigele et al, ; Sullivan et al, ).…”

Ein Gespür für Sauerstoff: Entdeckung des molekularen Mechanismus der zellulären Sauerstoffregulation rückt die Hydroxylierung von Makromolekülen in den Blickpunkt

“…In einer glücklichen Fügung für Ratcliffe beschäftigte sich eine andere Gruppe an der Universität Oxford um Christopher Schofield mit nicht-Häm Fe II -abhängigen Oxygenasen der Antibiotikabiosynthese und metabolischer Prozesse: [19] Diese Enzymklasse koppelt die Vier-Elektronen-Reduktion von molekularem Sauerstoff an die Oxidation sowohl des primären Substrats als auch die des Cosubstrats 2-Oxoglutarat (2OG). Vertreter dieser 2OG-abhängigen Dioxygenasen, die die Einführung oxidativer Modifikationen an Proteinen katalysieren, waren bereits bekannt, aufgrund von Arbeiten zur posttranslationalen Hydroxylierung von Lysin und Prolin im Kollagen oder auch Aspartyl-und Asparaginylhydroxylierung des epidermalen Wachstumsfaktors.…”