6MB5

AAC-IIIb binary with NEOMYCIN

6MB5 の概要

• エントリーDOI: 10.2210/pdb6mb5/pdb
• 分子名称: Aac(3)-IIIb protein, NEOMYCIN (3 entities in total)
• 機能のキーワード: acetyltransferase, promiscuity, gnat, antibiotic resistance, antibiotic, transferase-antibiotic complex, transferase/antibiotic
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29633.44

構造登録者

Cuneo, M.J.,Kumar, P. (登録日: 2018-08-29, 公開日: 2018-11-07, 最終更新日: 2024-03-13)

主引用文献

Kumar, P.,Selvaraj, B.,Serpersu, E.H.,Cuneo, M.J.
Encoding of Promiscuity in an Aminoglycoside Acetyltransferase.
J. Med. Chem., 61:10218-10227, 2018

PubMed Abstract: Aminoglycoside antibiotics are a large family of antibiotics that can be divided into two distinct classes on the basis of the substitution pattern of the central deoxystreptamine ring. Although aminoglycosides are chemically, structurally, and topologically diverse, some aminoglycoside-modifying enzymes (AGMEs) are able to inactivate as many as 15 aminoglycosides from the two main classes, the kanamycin- and neomycin-based antibiotics. Here, we present the crystal structure of a promiscuous AGME, aminoglycoside- N3-acetyltransferase-IIIb (AAC-IIIb), in the apo form, in binary drug (sisomicin, neomycin, and paromomycin) and coenzyme A (CoASH) complexes, and in the ternary neomycin-CoASH complex. These data provide a structural framework for interpretation of the thermodynamics of enzyme-ligand interactions and the role of solvent in the recognition of ligands. In combination with the recent structure of an AGME that does not have broad substrate specificity, these structures allow for the direct determination of how antibiotic promiscuity is encoded in some AGMEs.

PubMed: 30347146
DOI: 10.1021/acs.jmedchem.8b01393

実験手法

X-RAY DIFFRACTION (2.2 Å)