Sequence analysis and structure prediction of aminoglycoside-resistance 16S rRNA:m7G methyltransferases.
Methylation of G1405 within bacterial 16S ribosomal RNA results in high-level resistance to specific combinations of aminoglycoside antibiotics. Only a few closely related methyltransferases (MTases), which carry out the respective modification (here dubbed "Agr", for aminoglycoside resistance), are known. It is not clear, whether they are related to "typical" S-adenosylmethionine (AdoMet)-dependent MTases or not. Demydchuk et al., 1998 proposed that the cofactor-binding region is localized at the C-terminus of Agr MTases, which implies an interesting case of sequence permutation. Since the Agr MTases lack significant sequence similarity to other proteins, we tested that hypothesis using more sensitive sequence/structure threading approach. Structure prediction confirmed the presence of a putative AdoMet-binding site in these proteins, albeit at a distinct location, resembling that of "typical", non-permuted MTases. Additionally, a small alpha-helical domain dissimilar to other proteins in the database was identified in the N-terminal region of Agr MTases. Comparison of a three-dimensional model of the Agr family member with a recently solved structure of reovirus mRNA capping MTase suggests that the mechanism of guanine-N7 methylation in rRNA and mRNA may be different.
Bujnicki
J M
JM
Bioinformatics Laboratory, International Institute of Molecular and Cell Biology, Warsaw, Poland. iamb@bioinfo.pl
Rychlewski
L
L
D000192:Actinomycetales / Q000201:enzymology; D000595:Amino Acid Sequence; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005544:Forecasting; D008780:Methyltransferases / Q000737:chemistry* / Q000235:genetics; D008847:Micromonospora / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C446079:16S rRNA - m7G methyltransferase; D008780:Methyltransferases