6IX7

The structure of LepI C52A in complex with SAH and substrate analogue

6IX7 の概要

• エントリーDOI: 10.2210/pdb6ix7/pdb
• 分子名称: O-methyltransferase lepI, S-ADENOSYL-L-HOMOCYSTEINE, 4-hydroxy-3-[(2S,6E,8E)-2-methyldeca-6,8-dienoyl]-5-phenylpyridin-2(1H)-one, ... (7 entities in total)
• 機能のキーワード: leporin, sam, o-methyltransferase, pericyclase, biosynthetic protein
• 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: 93057.31

構造登録者

Cai, Y.,Ohashi, M.,Hai, Y.,Tang, Y.,Zhou, J. (登録日: 2018-12-09, 公開日: 2019-07-17, 最終更新日: 2023-11-22)

主引用文献

Cai, Y.,Hai, Y.,Ohashi, M.,Jamieson, C.S.,Garcia-Borras, M.,Houk, K.N.,Zhou, J.,Tang, Y.
Structural basis for stereoselective dehydration and hydrogen-bonding catalysis by the SAM-dependent pericyclase LepI.
Nat.Chem., 11:812-820, 2019

PubMed Abstract: LepI is an S-adenosylmethionine (SAM)-dependent pericyclase that catalyses the formation of the 2-pyridone natural product leporin C. Biochemical characterization has shown that LepI can catalyse stereoselective dehydration to yield a reactive (E)-quinone methide that can undergo bifurcating intramolecular Diels-Alder (IMDA) and hetero-Diels-Alder (HDA) cyclizations from an ambimodal transition state, as well as a [3,3]-retro-Claisen rearrangement to recycle the IMDA product into leporin C. Here, we solve the X-ray crystal structures of SAM-bound LepI and in complex with a substrate analogue, the product leporin C, and a retro-Claisen reaction transition-state analogue to understand the structural basis for the multitude of reactions. Structural and mutational analysis reveals how nature evolves a classic methyltransferase active site into one that can serve as a dehydratase and a multifunctional pericyclase. Catalysis of both sets of reactions employs H133 and R295, two active-site residues that are not found in canonical methyltransferases. An alternative role of SAM, which is not found to be in direct contact with the substrate, is also proposed.

PubMed: 31332284
DOI: 10.1038/s41557-019-0294-x

実験手法

X-RAY DIFFRACTION (1.835 Å)