8D7F

FlvF from Aspergillus flavus in complex with Bis-Tris

8D7F の概要

• エントリーDOI: 10.2210/pdb8d7f/pdb
• 分子名称: Terpene cyclase flvF, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, GLYCEROL (3 entities in total)
• 機能のキーワード: fungal protein, terpene cyclase fold, c-n bond formation, lyase
• 由来する生物種: Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC 167)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 342088.14

構造登録者

Tararina, M.A.,Christianson, D.W. (登録日: 2022-06-07, 公開日: 2022-09-07, 最終更新日: 2024-04-03)

主引用文献

Tararina, M.A.,Yee, D.A.,Tang, Y.,Christianson, D.W.
Structure of the Repurposed Fungal Terpene Cyclase FlvF Implicated in the C-N Bond-Forming Reaction of Flavunoidine Biosynthesis.
Biochemistry, 61:2014-2024, 2022

PubMed Abstract: The fungal species produces an alkaloid terpenoid, flavunoidine, through a hybrid biosynthetic pathway combining both terpene cyclase and nonribosomal peptide synthetase enzymes. Flavunoidine consists of a tetracyclic, oxygenated sesquiterpene core decorated with dimethyl cadaverine and 5,5-dimethyl-l-pipecolate moieties. Unique to the flavunoidine biosynthetic pathway is FlvF, a putative enzyme implicated in stereospecific C-N bond formation as dimethyl cadaverine is linked to the sesquiterpene core to generate pre-flavunoidine. Here, we report the 2.6 Å resolution crystal structure of FlvF, which adopts the α-helical fold of a class I terpene synthase. However, FlvF is not a terpene synthase, as indicated by its lack of enzymatic activity with farnesyl diphosphate and its lack of signature metal ion binding motifs that would coordinate to catalytic Mg ions. Thus, FlvF is the first example of a protein that adopts a terpene synthase fold but is not a terpene synthase. Two Bis-Tris molecules bind in the active site of FlvF, and the binding of these ligands guided the docking of pre-flavunoidine to generate a model of the enzyme-product complex. Phylogenetic analysis of FlvF and related fungal homologues reveals conservation of residues that interact with the tetracyclic sesquiterpene in this model, but less conservation of residues interacting with the pendant amino moiety. This may hint toward the possibility that alternative amino substrates can be linked to a common sesquiterpene core by FlvF homologues to generate flavunoidine congeners, such as the phospholipase C inhibitor hispidospermidin.

PubMed: 36037799
DOI: 10.1021/acs.biochem.2c00335

実験手法

X-RAY DIFFRACTION (2.62 Å)