6NP4

AAC-VIa bound to Tobramycin

6NP4 の概要

• エントリーDOI: 10.2210/pdb6np4/pdb
• 分子名称: Aminoglycoside N(3)-acetyltransferase, TOBRAMYCIN, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: antibiotic modifying enzyme, substrate selectivity, antibiotic, transferase
• 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: 29226.21

構造登録者

Kumar, P.,Cuneo, M.J. (登録日: 2019-01-17, 公開日: 2019-09-25, 最終更新日: 2023-10-11)

主引用文献

Kumar, P.,Agarwal, P.K.,Waddell, M.B.,Mittag, T.,Serpersu, E.H.,Cuneo, M.J.
Low-Barrier and Canonical Hydrogen Bonds Modulate Activity and Specificity of a Catalytic Triad.
Angew.Chem.Int.Ed.Engl., 58:16260-16266, 2019

PubMed Abstract: The position, bonding and dynamics of hydrogen atoms in the catalytic centers of proteins are essential for catalysis. The role of short hydrogen bonds in catalysis has remained highly debated and led to establishment of several distinctive geometrical arrangements of hydrogen atoms vis-à-vis the heavier donor and acceptor counterparts, that is, low-barrier, single-well or short canonical hydrogen bonds. Here we demonstrate how the position of a hydrogen atom in the catalytic triad of an aminoglycoside inactivating enzyme leads to a thirty-fold increase in catalytic turnover. A low-barrier hydrogen bond is present in the enzyme active site for the substrates that are turned over the best, whereas a canonical hydrogen bond is found with the least preferred substrate. This is the first comparison of these hydrogen bonds involving an identical catalytic network, while directly demonstrating how active site electrostatics adapt to the electronic nature of substrates to tune catalysis.

PubMed: 31515870
DOI: 10.1002/anie.201908535

実験手法

X-RAY DIFFRACTION (1.151 Å)