Erm proteins catalyze either monomethylation (type I) or dimethylation (type II) reactions at the exocyclic N6 position of a specific adenine residue (A2058, Escherichia coli rRNA nucleotide numbering) in 23S rRNA to reduce the affinity of MLSB antibiotics to the peptidyl transferase center, the most problematic MLSB-resistance mechanism adopted by many clinically selleck kinase inhibitor isolated, resistant

pathogens (Weisblum, 1995). KsgA, another posttranscriptional rRNA methylation enzyme, catalyzes two consecutive dimethylation reactions, resulting in two adjacent, dimethylated adenines at the 3′ end of 16S rRNA in bacteria (Helser et al., 1972; Poldermans et al., 1979; O’Farrell et al., 2004). In contrast to Erm, the inactivation of the ksgA gene confers resistance to the aminoglycoside antibiotic kasugamycin. KsgA enzymes and the resulting methylated adenine bases GKT137831 mouse appear to be conserved

in all three domains of life (O’Farrell et al., 2004; Xu et al., 2008; Park et al., 2009), while Erm is found in limited species of microorganisms that are considered to be either the target or the producers of MLSB antibiotics (Weisblum, 1995). This finding suggests that KsgA might be an essential enzyme for survival, but Erm is necessary only in the presence of antibiotic pressure. However, KsgA is not absolutely essential in bacteria. Mutant E. coli (i.e., KsgA−) exhibits a longer doubling Selleck Osimertinib time, but survival does not appear to be affected by mutation (O’Farrell et al., 2004). Recent studies have demonstrated that KsgA binds to translationally inactive 30S ribosomal subunits and acts as a checkpoint in ribosome biogenesis by ensuring that only mature small subunits proceed to translation (Desai and Rife, 2006; Connolly

et al., 2008; Mangat and Brown, 2008; Xu et al., 2008). On the other hand, the eukaryotic ortholog of KsgA, Dim1, is found to be essential in yeast, where its most important role is the cleavage of 33S pre-rRNA rather than rRNA methylation (Lafontaine et al., 1994, 1995; Pulicherla et al., 2009). The sequence homology between Erm and KsgA was first recognized in the mid-1980s (van Buul and van Knippenberg, 1985). These two protein families also have a very similar basic architecture; both consist of two domains, a conserved Rossman-fold N-terminal domain and a less-conserved C-terminal domain, and carry out very similar catalytic reactions (Yu et al., 1997; Schluckebier et al., 1999; O’Farrell et al., 2004). Recent crystal structures of Aquifex aeolicus KsgA in complex with RNA and cofactor revealed that Erm and KsgA showed a very similar mode in cofactor binding, but a different mode in the details of RNA binding (Tu et al., 2009).