7EHF

Crystal structure of the aminoglycoside resistance methyltransferase NpmB1

Summary for 7EHF

• Entry DOI: 10.2210/pdb7ehf/pdb
• Descriptor: 16S rRNA methyltransferase, SODIUM ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: 16s rrna methyltransferase, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 24349.24

Authors

Kawai, A.,Doi, Y. (deposition date: 2021-03-29, release date: 2021-08-11, Last modification date: 2023-11-29)

Primary citation

Kawai, A.,Suzuki, M.,Tsukamoto, K.,Minato, Y.,Doi, Y.
Functional and Structural Characterization of Acquired 16S rRNA Methyltransferase NpmB1 Conferring Pan-Aminoglycoside Resistance.
Antimicrob.Agents Chemother., 65:e0100921-e0100921, 2021

PubMed Abstract: Posttranslational methylation of the A site of 16S rRNA at position A1408 leads to pan-aminoglycoside resistance encompassing both 4,5- and 4,6-disubstituted 2-deoxystreptamine (DOS) aminoglycosides. To date, NpmA is the only acquired enzyme with such a function. Here, we present the function and structure of NpmB1, whose sequence was identified in Escherichia coli genomes registered from the United Kingdom. NpmB1 possesses 40% amino acid identity with NpmA1 and confers resistance to all clinically relevant aminoglycosides, including 4,5-DOS agents. Phylogenetic analysis of NpmB1 and NpmB2, its single-amino-acid variant, revealed that the encoding gene was likely acquired by E. coli from a soil bacterium. The structure of NpmB1 suggests that it requires a structural change of the β6/7 linker in order to bind to 16S rRNA. These findings establish NpmB1 and NpmB2 as the second group of acquired pan-aminoglycoside resistance 16S rRNA methyltransferases.

PubMed: 34310216
DOI: 10.1128/AAC.01009-21

Experimental method

X-RAY DIFFRACTION (1.5 Å)