6J1O

Crystal structure of a SAM-dependent methyltransferase LepI from Aspergillus flavus

6J1O の概要

• エントリーDOI: 10.2210/pdb6j1o/pdb
• 分子名称: O-methyltransferase lepI, S-ADENOSYLMETHIONINE, 5'-DEOXY-5'-METHYLTHIOADENOSINE, ... (4 entities in total)
• 機能のキーワード: complex, 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: 88120.53

構造登録者

Qiu, S.,Wei, C. (登録日: 2018-12-28, 公開日: 2019-05-01, 最終更新日: 2024-03-27)

主引用文献

Sun, Q.,Hu, Y.,Gu, Y.,Huang, J.,He, J.,Luo, L.,Yang, Y.,Yin, S.,Dou, C.,Wang, T.,Fu, X.,He, L.,Qi, S.,Zhu, X.,Yang, S.,Wei, X.,Cheng, W.
Deciphering the regulatory and catalytic mechanisms of an unusual SAM-dependent enzyme.
Signal Transduct Target Ther, 4:17-17, 2019

PubMed Abstract: -adenosyl-1-methionine (SAM)-dependent enzymes regulate various disease-related behaviors in all organisms. Recently, the leporin biosynthesis enzyme LepI, a SAM-dependent enzyme, was reported to catalyze pericyclic reactions in leporin biosynthesis; however, the mechanisms underlying LepI activation and catalysis remain unclear. This study aimed to investigate the molecular mechanisms of LepI. Here, we reported crystal structures of LepI bound to SAM/5'-deoxy-5'-(methylthio) adenosine (MTA), -adenosyl-homocysteine (SAH), and SAM/substrate states. Structural and biochemical analysis revealed that MTA or SAH inhibited the enzyme activities, whereas SAM activated the enzyme. The analysis of the substrate-bound structure of LepI demonstrated that this enzymatic retro-Claisen rearrangement was primarily driven by three critical polar residues His133, Arg197, Arg295 around the active site and assisted by SAM with unclear mechanism. The present studies indicate that the unique mechanisms underlying regulatory and catalysis of the unusual SAM-dependent enzyme LepI, not only strengthening current understanding of the fundamentally biochemical catalysis, but also providing novel insights into the design of SAM-dependent enzyme-specific small molecules.

PubMed: 31149354
DOI: 10.1038/s41392-019-0052-y

実験手法

X-RAY DIFFRACTION (1.7 Å)