9GL0

Crystal Structure of Acetylpolyamine aminohydrolase (ApaH) from Legionella pneumophila

9GL0 の概要

• エントリーDOI: 10.2210/pdb9gl0/pdb
• 分子名称: Acetylpolyamine aminohydrolase, ZINC ION, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: deacetylase, deacylase, hydrolase
• 由来する生物種: Legionella pneumophila
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 201364.60

構造登録者

Graf, L.G.,Schulze, S.,Palm, G.J.,Lammers, M. (登録日: 2024-08-26, 公開日: 2024-11-06, 最終更新日: 2024-11-13)

主引用文献

Graf, L.G.,Moreno-Yruela, C.,Qin, C.,Schulze, S.,Palm, G.J.,Schmoker, O.,Wang, N.,Hocking, D.M.,Jebeli, L.,Girbardt, B.,Berndt, L.,Dorre, B.,Weis, D.M.,Janetzky, M.,Albrecht, D.,Zuhlke, D.,Sievers, S.,Strugnell, R.A.,Olsen, C.A.,Hofmann, K.,Lammers, M.
Distribution and diversity of classical deacylases in bacteria.
Nat Commun, 15:9496-9496, 2024

PubMed Abstract: Classical Zn-dependent deac(et)ylases play fundamental regulatory roles in life and are well characterized in eukaryotes regarding their structures, substrates and physiological roles. In bacteria, however, classical deacylases are less well understood. We construct a Generalized Profile (GP) and identify thousands of uncharacterized classical deacylases in bacteria, which are grouped into five clusters. Systematic structural and functional characterization of representative enzymes from each cluster reveal high functional diversity, including polyamine deacylases and protein deacylases with various acyl-chain type preferences. These data are supported by multiple crystal structures of enzymes from different clusters. Through this extensive analysis, we define the structural requirements of substrate selectivity, and discovered bacterial de-D-/L-lactylases and long-chain deacylases. Importantly, bacterial deacylases are inhibited by archetypal HDAC inhibitors, as supported by co-crystal structures with the inhibitors SAHA and TSA, and setting the ground for drug repurposing strategies to fight bacterial infections. Thus, we provide a systematic structure-function analysis of classical deacylases in bacteria and reveal the basis of substrate specificity, acyl-chain preference and inhibition.

PubMed: 39489725
DOI: 10.1038/s41467-024-53903-0

実験手法

X-RAY DIFFRACTION (2.7 Å)