Please use this identifier to cite or link to this item:
Title: Crystal structure and functional analysis of mycobacterial erythromycin resistance methyltransferase Erm38 reveals its RNA-binding site
Authors: Goh, Boon Chong
Xiang, Xinyu
Lescar, Julien
Dedon, Peter C.
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Goh, B. C., Xiang, X., Lescar, J. & Dedon, P. C. (2022). Crystal structure and functional analysis of mycobacterial erythromycin resistance methyltransferase Erm38 reveals its RNA-binding site. Journal of Biological Chemistry, 298(2), 101571-.
Project: ING-000772 BIO IGN
H19H0G1003/TOR 005–018
Journal: Journal of Biological Chemistry
Abstract: Erythromycin resistance methyltransferases (Erms) confer resistance to macrolide, lincosamide, and streptogramin antibiotics in Gram-positive bacteria and mycobacteria. Although structural information for ErmAM, ErmC, and ErmE exists from Gram-positive bacteria, little is known about the Erms in mycobacteria, as there are limited biochemical data and no structures available. Here, we present crystal structures of Erm38 from Mycobacterium smegmatis in apoprotein and cofactor-bound forms. Based on structural analysis and mutagenesis, we identified several catalytically critical, positively charged residues at a putative RNA-binding site. We found that mutation of any of these sites is sufficient to abolish methylation activity, whereas the corresponding RNA-binding affinity of Erm38 remains unchanged. The methylation reaction thus appears to require a precise ensemble of amino acids to accurately position the RNA substrate, such that the target nucleotide can be methylated. In addition, we computationally constructed a model of Erm38 in complex with a 32-mer RNA substrate. This model shows the RNA substrate stably bound to Erm38 by a patch of positively charged residues. Furthermore, a π-π stacking interaction between a key aromatic residue of Erm38 and a target adenine of the RNA substrate forms a critical interaction needed for methylation. Taken together, these data provide valuable insights into Erm-RNA interactions, which will aid subsequent structure-based drug design efforts.
ISSN: 0021-9258
DOI: 10.1016/j.jbc.2022.101571
Schools: School of Biological Sciences 
Research Centres: NTU Institute of Structural Biology 
Rights: © 2022 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Citations 50

Updated on Oct 3, 2023

Web of ScienceTM
Citations 50

Updated on Oct 4, 2023

Page view(s)

Updated on Oct 4, 2023


Updated on Oct 4, 2023

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.