7EHE

Acetolactate Synthase from Trichoderma harzianum

7EHE の概要

• エントリーDOI: 10.2210/pdb7ehe/pdb
• 分子名称: Acetolactate synthase, MAGNESIUM ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: acetolactate synthase, bgc, harzianic acid, transferase
• 由来する生物種: Trichoderma harzianum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 152553.60

構造登録者

Zang, X.,Tang, Y.,Zhou, J. (登録日: 2021-03-29, 公開日: 2021-06-30, 最終更新日: 2023-11-29)

主引用文献

Xie, L.,Zang, X.,Cheng, W.,Zhang, Z.,Zhou, J.,Chen, M.,Tang, Y.
Harzianic Acid from Trichoderma afroharzianum Is a Natural Product Inhibitor of Acetohydroxyacid Synthase.
J.Am.Chem.Soc., 2021

PubMed Abstract: Acetohydroxyacid synthase (AHAS) is the first enzyme in the branched-chain amino acid biosynthetic pathway and is a validated target for herbicide and fungicide development. Here we report harzianic acid (HA, ) produced by the biocontrol fungus t-22 (Tht22) as a natural product inhibitor of AHAS. The biosynthetic pathway of HA was elucidated with heterologous reconstitution. Guided by a putative self-resistance enzyme in the genome, HA was biochemically demonstrated to be a selective inhibitor of fungal AHAS, including those from phytopathogenic fungi. In addition, HA can inhibit a common resistant variant of AHAS in which the active site proline is mutated. Structural analysis of AHAS complexed with HA revealed the molecular basis of competitive inhibition, which differs from all known commercial AHAS inhibitors. The alternative binding mode also rationalizes the selectivity of HA, as well as effectiveness toward resistant mutants. A proposed role of HA biosynthesis by Tht22 in the rhizosphere is discussed based on the data.

PubMed: 34132537
DOI: 10.1021/jacs.1c03988

実験手法

X-RAY DIFFRACTION (2.28 Å)