The 2.2 angstrom structure of the rRNA methyltransferase ErmC ' and its complexes with cofactor and cofactor analogs: Implications for the reaction mechanism
C. Schluckebier et al., The 2.2 angstrom structure of the rRNA methyltransferase ErmC ' and its complexes with cofactor and cofactor analogs: Implications for the reaction mechanism, J MOL BIOL, 289(2), 1999, pp. 277-291
The rRNA methyltransferase ErmC' transfers methyl groups from S-adenosyl-L-
methionine to atom N6 of an adenine base within the peptidyltransferase loo
p of 23 S rRNA, thus conferring antibiotic resistance against a number of m
acrolide antibiotics. The crystal structures of ErmC' and of its complexes
with the cofactor S-adenosyl-L-methionine, the reaction product S-adenosyl-
L-homocysteine and the methyltransferase inhibitor Sinefungin, respectively
, show that the enzyme undergoes small conformational changes upon ligand b
inding. Overall, the ligand molecules bind to the protein in a similar mode
as observed for other methyltransferases. Small differences between the bi
nding of the amino acid parts of the different ligands are correlated with
differences in their chemical structure. A model for the transition-state b
ased on the atomic details of the active site is consistent with a one-step
methyl-transfer mechanism and might serve as a first step towards the desi
gn of potent Erm inhibitors. (C) 1999 Academic Press.