Crystal Structure of ErmC', an rRNA Methyltransferase Which Mediates Antibiotic Resistance in Bacteria

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• 作者：Dirksen E. Bussiere ; Steven W. Muchmore ; Christopher G. Dealwis ; Gerd Schluckebier ; Vicki L. Nienaber ; Rohinton P. Edalji ; Karl A. Walter ; Uri S. Ladror ; Thomas F. Holzman ; and Cele Abad-Zapatero
• 刊名：Biochemistry
• 出版年：1998
• 出版时间：May 19, 1998
• 年：1998
• 卷：37
• 期：20
• 页码：7103 - 7112
• 全文大小：223K
• 年卷期：v.37,no.20(May 19, 1998)
• ISSN：1520-4995

文摘

The prevalent mechanism of bacterial resistance to erythromycinand other antibiotics of themacrolide-lincosamide-streptogramin B group (MLS) is methylation ofthe 23S rRNA component ofthe 50S subunit in bacterial ribosomes. This sequence-specificmethylation is catalyzed by the Erm groupof methyltransferases (MTases). They are found in several strainsof pathogenic bacteria, and ErmC isthe most studied member of this class. The crystal structure ofErmC' (a naturally occurring variant ofErmC) from Bacillus subtilis has been determined at 3.0 Åresolution by multiple anomalous diffractionphasing methods. The structure consists of a conserved /amino-terminal domain which binds thecofactor S-adenosyl-L-methionine (SAM), followedby a smaller, -helical RNA-recognition domain. The-sheet structure of the SAM-binding domain is well-conserved betweenthe DNA, RNA, and small-molecule MTases. However, the C-terminal nucleic acid bindingdomain differs from the DNA-bindingdomains of other MTases and is unlike any previously reportedRNA-recognition fold. A large, positivelycharged, concave surface is found at the interface of the N- andC-terminal domains and is proposed toform part of the protein-RNA interaction surface. ErmC' exhibitsthe conserved structural motifspreviously found in the SAM-binding domain of other methyltransferases.A model of SAM bound toErmC' is presented which is consistent with the motif conservationamong MTases.