The prevalent mechanism o
f bacterial resistance to erythromycinand other antibiotics o
f themacrolide-lincosamide-streptogramin B group (MLS) is methylation o
fthe 23S rRNA component o
fthe 50S subunit in bacterial ribosomes. This sequence-speci
ficmethylation is catalyzed by the Erm groupo
f methyltrans
ferases (MTases). They are
found in several strainso
f pathogenic bacteria, and ErmC isthe most studied member o
f this class. The crystal structure o
fErmC' (a naturally occurring variant o
fErmC)
from
Bacillus subtilis has been determined at 3.0 Åresolution by multiple anomalous di
ffractionphasing methods. The structure consists o
f a conserved
fchars/alpha.gi
f" BORDER=0>/
fchars/beta2.gi
f" BORDER=0 ALIGN="middle">amino-terminal domain which binds theco
factor
S-adenosyl-
L-methionine (SAM),
followedby a smaller,
fchars/alpha.gi
f" BORDER=0>-helical RNA-recognition domain. The
fchars/beta2.gi
f" BORDER=0 ALIGN="middle">-sheet structure o
f the SAM-binding domain is well-conserved betweenthe DNA, RNA, and small-molecule MTases. However, the C-terminal nucleic acid bindingdomain di
ffers
from the DNA-bindingdomains o
f other MTases and is unlike any previously reportedRNA-recognition
fold. A large, positivelycharged, concave sur
face is
found at the inter
face o
f the N- andC-terminal domains and is proposed to
form part o
f the protein-RNA interaction sur
face. ErmC' exhibitsthe conserved structural moti
fspreviously
found in the SAM-binding domain o
f other methyltrans
ferases.A model o
f SAM bound toErmC' is presented which is consistent with the moti
f conservationamong MTases.