RRNA chemical modification

Fig.4. 13 Blasticidin S. Blasticidin S (purple) base pairs to the P-loop of rRNA (grey). Its guanidinium tail forms hydrogen bonds (dotted lines) to the phosphate and stacks hydrophobically onto the base of Hm A2474, a nucleotide that is protected from chemical modification (green) by blasticidin S. Superimposition of rRNA between crystal structures causes blasticidin S to become superimposed on C74 and C75 (yellow) of the analogue of a CCA end of tRNA. Fig. from [7].

Figure 9 Aminoglycoside antibiotic modifying enzymes. The aminoglycoside antibiotics such as kanamycin B (shown) bind to the 16 S rRNA of the bacterial ribosome impairing cognate codon-anticodon discrimination (A). Resistance occurs via acetylation (AAC), phosphorylation (APH), or adenylylation (ANT) of the antibiotic (B). A wide variety of enzymes are known with different regiospecificities of chemical modification, and the sites of some clinically important enzymes are shown in panel C.

Figure 11 Chemical modification of Type B streptogramins. These antibiotics bind to the large ribosome adjacent to the chloramphenicol binding site (A). A key interaction with the 23 S rRNA is blocked by the action of VAT-dependent acetylation (B).

Figure 12 Macrolide modifying enzymes. Macrolide antibiotics such as erythromycin (shown) bind to the large ribosomal subunit through interactions with the 23 S rRNA (A). Chemical modification of the essential desosamine sugar blocks ribosome binding (B).

Fig. 2. The peptidyltransferase center. The structure of the central loop of Domain V of E. coli 23S rRNA is shown. Nucleotides involved in resistance against different inhibitors are indicated. Closed symbols indicate resistance and open symbols protection against chemical modification by bound antibiotic. Mutations that confer resistance to anisomycin in archaea are indicated [87] (Hcu, Halobacterium cutirubrum Hha, H. halobium). The presence of either a G or U at position 2058 in archaea is also indicated. As a consequence of this change archaea are resistant to erythromycin (Hmo, Halococcus morrhuae, Mva, Methanococcus vannielii Tte, Thermoproteus lenax Dmo, Desulfurococcus wofirfo) [29,30,88,90]. Positions where crosslinking to photoreactive derivatives of Phe-tRNA and puromycin have been observed as well as nucleotides protected by bound tRNA are also indicated. Modified from ref [73].

A FIGURE 12-34 Processing of pre-rRNA and assembly of ribosomes in higher eukaryotes. Ribosomal and nucleolar proteins associate with 45S pre-RNA as it is synthesized, forming an SOS pre-rRNR Sites of cleavage and chemical modifications are determined by small nucleolar RNAs (not shown). Note that synthesis of 5S rRNA occurs outside the nucleolus. 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

Processing refers to modification of the primary transcripts formed by RNA polymerase. In bacteria, it is restricted to the transcripts that contain rRNA and tRNA. In these cases, larger transcripts are chemically modified and then cut down to the smaller, mature forms of rRNA and tRNA by... 

Oligonucleotides can undergo covalent modifications. [202] These can be natural ones such as those present in tRNA and rRNA but they can also result from reactions with exogenous substances and are the markers indicating possible degradations of the cells. They also can be modified chemically to create new drugs. Almost all these modifications are accompanied by variations in mass, and mass spectrometry is thus useful to identify their nature and position in the sequence. [203-205]... 

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