6BBZ

Room temperature neutron/X-ray structure of sisomicin bound AAC-VIa

6BBZ の概要

• エントリーDOI: 10.2210/pdb6bbz/pdb
• 関連するPDBエントリー: 6BBR
• 分子名称: AAC 3-VI protein, (1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl 3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: acetyltransferase, transferase-antibiotic complex, transferase/antibiotic
• 由来する生物種: Enterobacter cloacae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32816.29

構造登録者

Cuneo, M.J.,Kumar, P. (登録日: 2017-10-20, 公開日: 2018-02-28, 最終更新日: 2023-10-04)

主引用文献

Kumar, P.,Serpersu, E.H.,Cuneo, M.J.
A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad.
Sci Adv, 4:eaas8667-eaas8667, 2018

PubMed Abstract: One group of enzymes that confer resistance to aminoglycoside antibiotics through covalent modification belongs to the GCN5-related -acetyltransferase (GNAT) superfamily. We show how a unique GNAT subfamily member uses a previously unidentified noncanonical catalytic triad, consisting of a glutamic acid, a histidine, and the antibiotic substrate itself, which acts as a nucleophile and attacks the acetyl donor molecule. Neutron diffraction studies allow for unambiguous identification of a low-barrier hydrogen bond, predicted in canonical catalytic triads to increase basicity of the histidine. This work highlights the role of this unique catalytic triad in mediating antibiotic resistance while providing new insights into the design of the next generation of aminoglycosides.

PubMed: 29632894
DOI: 10.1126/sciadv.aas8667

実験手法

NEUTRON DIFFRACTION (2.2 Å)
X-RAY DIFFRACTION (1.9 Å)