Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance.
The Erm family of methyltransferases is responsible for the development of resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics. These enzymes methylate an adenine of 23S ribosomal RNA that prevents the MLS antibiotics from binding to the ribosome and exhibiting their antibacterial activity. Here we describe the three-dimensional structure of an Erm family member, ErmAM, as determined by NMR spectroscopy. The catalytic domain of ErmAM is structurally similar to that found in other methyltransferases and consists of a seven-stranded beta-sheet flanked by alpha-helices and a small two-stranded beta-sheet. In contrast to the catalytic domain, the substrate binding domain is different from other methyltransferases and adopts a novel fold that consists of four alpha-helices.
Yu
L
L
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Petros
A M
AM
Schnuchel
A
A
Zhong
P
P
Severin
J M
JM
Walter
K
K
Holzman
T F
TF
Fesik
S W
SW
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D004352:Drug Resistance, Microbial / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000737:chemistry; D055231:Lincosamides; D018942:Macrolides / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D014769:Virginiamycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D055231:Lincosamides; D018942:Macrolides; D014769:Virginiamycin; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase