6INW

A Pericyclic Reaction enzyme

6INW の概要

• エントリーDOI: 10.2210/pdb6inw/pdb
• 分子名称: O-methyltransferase lepI, S-ADENOSYLMETHIONINE (3 entities in total)
• 機能のキーワード: dimer, alpha helical, two-domain, transferase
• 由来する生物種: Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / NRRL 3357 / JCM 12722 / SRRC 167)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89309.67

構造登録者

Feng, Y.,Chang, M.,Wang, H.,Liu, Z.,Zhou, Y. (登録日: 2018-10-28, 公開日: 2019-07-03, 最終更新日: 2024-11-13)

主引用文献

Chang, M.,Zhou, Y.,Wang, H.,Liu, Z.,Zhang, Y.,Feng, Y.
Crystal structure of the multifunctional SAM-dependent enzyme LepI provides insights into its catalytic mechanism.
Biochem.Biophys.Res.Commun., 515:255-260, 2019

PubMed Abstract: Pericyclic reactions are among the most powerful synthetic transformations widely applied in the synthesis of multiple regioselective and stereoselective carbon-carbon bonds. LepI is a recently identified S-adenosyl-l-methionine (SAM)-dependent enzyme, which could catalyze dehydration, Diels-Alder reaction, and the retro-Claisen rearrangement reactions. However, the mechanism underlying these reactions by LepI remains elusive. Here we report the structure of LepI in complex with SAM as its co-factor, which adopts a typical class I methyltransferase fold. Docking studies are performed to investigate the binding modes of various substrates/products and provide insights into the catalytic mechanism of the multiple reactions catalyzed by LepI. Our study suggests that the dehydration reaction may start from the deprotonation of the hydroxyl group on the pyridone ring of the substrate by LepI, during which R295 and D296 play important roles in substrate binding and stabilizing the reaction intermediate. The stereoselective dehydration is accomplished through the trans-conformer of the leaving alcohol group which is trapped by nearby residues. The pericyclic reactions following dehydration are facilitated by the hydrophobic and hydrophilic interactions in the binding pocket. H133 and R295, two residues not conserved in other methyltransferases, might account for the unique activity of LepI among the SAM-dependent methyltransferase family. Together, this study provides important structural insights into the unique reactions catalyzed by LepI and will shed light on the knowledge of mechanisms of pericyclic reactions.

PubMed: 31101338
DOI: 10.1016/j.bbrc.2019.05.031

実験手法

X-RAY DIFFRACTION (1.798 Å)