Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones

Abstract

After publication of the original article, three errors were discovered in Figure 2 and its legend. In Figure 2A, the dATP curve was described as red and the dGTP curve as blue; in fact, the dATP curve is blue and the dGTP curve is red. In Figure 2C, the dATP and dGTP curves were colored incorrectly, i.e., dATP in red and dGTP in blue. This was inconsistent with the coloring of the other panels. Finally, in the legend for Figure 2E, the colors of the curves were also wrongly described, as in Figure 2A. The figure and legend have been corrected in the online version of the article, and the corrected figure and legend are also printed below. These errors do not affect the interpretation of the data. The authors apologize for any confusion this may have caused.

Acetylation regulates ribonucleotide reductase activity and cancer cell growth

“…RNR plays a critical role in regulating the total rate of DNA synthesis, so that DNA to cell mass is maintained at a constant ratio during cell division and DNA repair 3 . RNR enzymes are divided into three classes termed class I, class II, and class III, based on how radicals are generated during the reaction 4 . Class I is the most extensively studied RNR and is present in all eukaryotes and some prokaryotes 3 .…”

“…RRM1 is the regulatory subunit harboring two allosteric sites for its regulation 5–7 . RRM2 generates a stable tyrosine radical which is transferred to RRM1 cysteine residues to initiate the reduction reaction upon binding of the substrate 4,5 . In addition, p53R2 is encoded by the RRM2B gene, is induced by p53, and has been identified as a second radical-providing small subunit in mammalian cells 8 .…”

“…RNR is allosterically regulated at two levels influencing overall activity and substrate specificity 4,7 . The overall activity is regulated by binding of ATP (stimulatory) or dATP (inhibitory) to the activity site (A site) on the RRM1 subunit 7 .…”

Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade and the role of insertions and extensions in diversification

“…Many of these class Ic-like sequences are found in the NrdAz and NrdAq clades ( Figure 6B , light blue branches). The NrdAz clade is also notable for having many subclades and a high occurrence of sequences with multiple ATP-cones, such as the P. aeruginosa class Ia RNR and Chlamydia trachomatis class Ic RNR, which have 2 and 3 ATP-cones, respectively ( Figure 6B , Pa and Ct ) (Johansson et al, 2016b; Roshick et al, 2000; Torrents et al, 2006). As discussed in our SSN analysis of ATP cones ( Figure 5B , NrdAz), the N-terminal copy within the tandem ATP-cones in NrdAz sequences is most homologous to the ancestral ATP-cone motif.…”

“…Likewise, the third copies (Figure 5A, gray hexagonal nodes in spoke 3) extend out of the cluster of second copies. Previously, it was demonstrated with the two tandem ATP-cones of Pseudomonas aeruginosa class Ia RNR that only the N-terminal copy is functional, while the second copy is unable to bind ligands (Johansson et al, 2016a). Based on this finding, it was proposed that the N-terminal copy was acquired to regain allosteric regulation after the inner copy had lost function due to sequence degradation.…”