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Structural and Molecular Dynamics Analysis of Plant Serotonin N ‐Acetyltransferase Reveal an Acid/Base‐Assisted Catalysis in Melatonin Biosynthesis
Author(s) -
Liao Lijing,
Zhou Yuanze,
Xu Youdong,
Zhang Yuhao,
Liu Xikai,
Liu Biao,
Chen Xinxin,
Guo Yan,
Zeng Zhixiong,
Zhao Yucheng
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202100992
Subject(s) - acetyltransferase , biosynthesis , transferase , chemistry , biochemistry , stereochemistry , mutagenesis , serotonin , active site , enzyme , biology , acetylation , mutation , gene , receptor
Serotonin N‐acetyltransferase (SNAT) is the key rate‐limiting enzyme in melatonin biosynthesis. It mediates melatonin biosynthesis in plants by using serotonin and 5‐methoxytryptamine (5‐MT), but little is known of its underlying mechanisms. Herein, we present a detailed reaction mechanism of a SNAT from Oryza sativa through combined structural and molecular dynamics (MD) analysis. We report the crystal structures of plant SNAT in the apo and binary/ternary complex forms with acetyl‐CoA (AcCoA), serotonin, and 5‐MT. OsSNAT exhibits a unique enzymatically active dimeric fold not found in the known structures of arylalkylamine N‐acetyltransferase (AANAT) family. The key residues W188, D189, D226, N220, and Y233 located around the active pocket are important in catalysis, confirmed by site‐directed mutagenesis. Combined with MD simulations, we hypothesize a novel plausible catalytic mechanism in which D226 and Y233 function as catalytic base and acid during the acetyl‐transfer reaction.