6EDV

Structure of a GNAT superfamily acetyltransferase PA3944 in complex with CoA

6EDV の概要

• エントリーDOI: 10.2210/pdb6edv/pdb
• 関連するPDBエントリー: 6EDD
• 分子名称: Acetyltransferase PA3944, CALCIUM ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: gcn5-related n-acetyltransferase, gnat, pseudomonas aeruginosa, structural genomics, psi-biology, center for structural genomics of infectious diseases, csgid, transferase
• 由来する生物種: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23011.79

構造登録者

Majorek, K.A.,Satchell, K.J.F.,Joachimiak, A.,Minor, W.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2018-08-12, 公開日: 2018-12-26, 最終更新日: 2023-10-11)

主引用文献

Czub, M.P.,Zhang, B.,Chiarelli, M.P.,Majorek, K.A.,Joe, L.,Porebski, P.J.,Revilla, A.,Wu, W.,Becker, D.P.,Minor, W.,Kuhn, M.L.
A Gcn5-Related N-Acetyltransferase (GNAT) Capable of Acetylating Polymyxin B and Colistin Antibiotics in Vitro.
Biochemistry, 57:7011-7020, 2018

PubMed Abstract: Deeper exploration of uncharacterized Gcn5-related N-acetyltransferases has the potential to expand our knowledge of the types of molecules that can be acylated by this important superfamily of enzymes and may offer new opportunities for biotechnological applications. While determining native or biologically relevant in vivo functions of uncharacterized proteins is ideal, their alternative or promiscuous in vitro capabilities provide insight into key active site interactions. Additionally, this knowledge can be exploited to selectively modify complex molecules and reduce byproducts when synthetic routes become challenging. During our exploration of uncharacterized Gcn5-related N-acetyltransferases from Pseudomonas aeruginosa, we identified such an example. We found that the PA3944 enzyme acetylates both polymyxin B and colistin on a single diaminobutyric acid residue closest to the macrocyclic ring of the antimicrobial peptide and determined the PA3944 crystal structure. This finding is important for several reasons. (1) To the best of our knowledge, this is the first report of enzymatic acylation of polymyxins and thus reveals a new type of substrate that this enzyme family can use. (2) The enzymatic acetylation offers a controlled method for antibiotic modification compared to classical promiscuous chemical methods. (3) The site of acetylation would reduce the overall positive charge of the molecule, which is important for reducing nephrotoxic effects and may be a salvage strategy for this important class of antibiotics. While the physiological substrate for this enzyme remains unknown, our structural and functional characterization of PA3944 offers insight into its unique noncanonical substrate specificity.

PubMed: 30499668
DOI: 10.1021/acs.biochem.8b00946

実験手法

X-RAY DIFFRACTION (1.35 Å)