Crystal structure of ErmE - 23S rRNA methyltransferase in macrolide resistance

Autor:	Maria Selmer, Alena Stsiapanava
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Stereochemistry Glycine lcsh:Medicine 010402 general chemistry Antimicrobial resistance Arginine Crystallography X-Ray 01 natural sciences Ribosome Article Substrate Specificity 03 medical and health sciences 23S ribosomal RNA Structural Biology Catalytic Domain Drug Resistance Bacterial Transferase Fluorometry Binding site lcsh:Science X-ray crystallography Strukturbiologi Cofactor binding Multidisciplinary Binding Sites biology Chemistry lcsh:R Methyltransferases biology.organism_classification Macrolide binding Protein tertiary structure 0104 chemical sciences Enzymes Anti-Bacterial Agents RNA Bacterial RNA Ribosomal 23S 030104 developmental biology Saccharopolyspora erythraea lcsh:Q Macrolides Saccharopolyspora
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) 'Scientific Reports ', vol: 9, pages: 14607-1-14607-9 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-51174-0
Popis:	Pathogens often receive antibiotic resistance genes through horizontal gene transfer from bacteria that produce natural antibiotics. ErmE is a methyltransferase (MTase) from Saccharopolyspora erythraea that dimethylates A2058 in 23S rRNA using S-adenosyl methionine (SAM) as methyl donor, protecting the ribosomes from macrolide binding. To gain insights into the mechanism of macrolide resistance, the crystal structure of ErmE was determined to 1.75 Å resolution. ErmE consists of an N-terminal Rossmann-like α/ß catalytic domain and a C-terminal helical domain. Comparison with ErmC’ that despite only 24% sequence identity has the same function, reveals highly similar catalytic domains. Accordingly, superposition with the catalytic domain of ErmC’ in complex with SAM suggests that the cofactor binding site is conserved. The two structures mainly differ in the C-terminal domain, which in ErmE contains a longer loop harboring an additional 310 helix that interacts with the catalytic domain to stabilize the tertiary structure. Notably, ErmE also differs from ErmC’ by having long disordered extensions at its N- and C-termini. A C-terminal disordered region rich in arginine and glycine is also a present in two other MTases, PikR1 and PikR2, which share about 30% sequence identity with ErmE and methylate the same nucleotide in 23S rRNA.
Databáze:	OpenAIRE
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