4DMO

Crystal structure of the (BACCR)NAT3 arylamine N-acetyltransferase from Bacillus cereus reveals a unique Cys-His-Glu catalytic triad

4DMO の概要

• エントリーDOI: 10.2210/pdb4dmo/pdb
• 分子名称: N-hydroxyarylamine O-acetyltransferase, 3-(1-methylpiperidinium-1-yl)propane-1-sulfonate (3 entities in total)
• 機能のキーワード: acetyltransferase, transferase
• 由来する生物種: Bacillus cereus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60863.97

構造登録者

Kubiak, X.,Li de la Sierra-Gallay, I.,Haouz, A.,Weber, P.,Rodrigues-Lima, F. (登録日: 2012-02-08, 公開日: 2013-06-26, 最終更新日: 2023-09-13)

主引用文献

Kubiak, X.,Li de la Sierra-Gallay, I.,Chaffotte, A.F.,Pluvinage, B.,Weber, P.,Haouz, A.,Dupret, J.M.,Rodrigues-Lima, F.
Structural and Biochemical Characterization of an Active Arylamine N-Acetyltransferase Possessing a Non-canonical Cys-His-Glu Catalytic Triad.
J.Biol.Chem., 288:22493-22505, 2013

PubMed Abstract: Arylamine N-acetyltransferases (NATs), a class of xenobiotic-metabolizing enzymes, catalyze the acetylation of aromatic amine compounds through a strictly conserved Cys-His-Asp catalytic triad. Each residue is essential for catalysis in both prokaryotic and eukaryotic NATs. Indeed, in (HUMAN)NAT2 variants, mutation of the Asp residue to Asn, Gln, or Glu dramatically impairs enzyme activity. However, a putative atypical NAT harboring a catalytic triad Glu residue was recently identified in Bacillus cereus ((BACCR)NAT3) but has not yet been characterized. We report here the crystal structure and functional characterization of this atypical NAT. The overall fold of (BACCR)NAT3 and the geometry of its Cys-His-Glu catalytic triad are similar to those present in functional NATs. Importantly, the enzyme was found to be active and to acetylate prototypic arylamine NAT substrates. In contrast to (HUMAN) NAT2, the presence of a Glu or Asp in the triad of (BACCR)NAT3 did not significantly affect enzyme structure or function. Computational analysis identified differences in residue packing and steric constraints in the active site of (BACCR)NAT3 that allow it to accommodate a Cys-His-Glu triad. These findings overturn the conventional view, demonstrating that the catalytic triad of this family of acetyltransferases is plastic. Moreover, they highlight the need for further study of the evolutionary history of NATs and the functional significance of the predominant Cys-His-Asp triad in both prokaryotic and eukaryotic forms.

PubMed: 23770703
DOI: 10.1074/jbc.M113.468595

実験手法

X-RAY DIFFRACTION (2.14 Å)