6MN4

Crystal structure of aminoglycoside acetyltransferase AAC(3)-IVa, H154A mutant, in complex with apramycin

6MN4 の概要

• エントリーDOI: 10.2210/pdb6mn4/pdb
• 分子名称: Aminoglycoside N(3)-acetyltransferase, AAC(3)-IVa, APRAMYCIN, ZINC ION, ... (8 entities in total)
• 機能のキーワード: antibiotic_nat family, acetyltransferase, aminoglycoside, antibiotic resistance, coenzyme a, apramycin, aac(3)-iva, csgid, transferase, center for structural genomics of infectious diseases, national institute of allergy and infectious diseases, niaid, transferase-antibiotic complex, transferase/antibiotic
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 174397.77

構造登録者

Stogios, P.J.,Evdokimova, E.,Michalska, K.,Di Leo, R.,Savchenko, A.,Joachimiak, A.,Satchell, K.J.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2018-10-01, 公開日: 2018-10-24, 最終更新日: 2023-10-11)

主引用文献

Stogios, P.J.,Bordeleau, E.,Xu, Z.,Skarina, T.,Evdokimova, E.,Chou, S.,Diorio-Toth, L.,D'Souza, A.W.,Patel, S.,Dantas, G.,Wright, G.D.,Savchenko, A.
Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family.
Commun Biol, 5:263-263, 2022

PubMed Abstract: The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment.

PubMed: 35338238
DOI: 10.1038/s42003-022-03219-w

実験手法

X-RAY DIFFRACTION (2.8 Å)