6OH7

Crystal structure of (E)-biformene synthase LrdC from Streptomyces sp. strain K155 in complex with Mg

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6OH7 の概要

• エントリーDOI: 10.2210/pdb6oh7/pdb
• 分子名称: Labdane-related diterpene synthase, DI(HYDROXYETHYL)ETHER, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: bioactive natural products, biformene, diterpene synthase, labdatriene, lyase
• 由来する生物種: Streptomyces sp.
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37859.06

構造登録者

Centeno-Leija, S.,Serrano-Posada, H. (登録日: 2019-04-04, 公開日: 2019-04-17, 最終更新日: 2024-04-03)

主引用文献

Centeno-Leija, S.,Tapia-Cabrera, S.,Guzman-Trampe, S.,Esquivel, B.,Esturau-Escofet, N.,Tierrafria, V.H.,Rodriguez-Sanoja, R.,Zarate-Romero, A.,Stojanoff, V.,Rudino-Pinera, E.,Sanchez, S.,Serrano-Posada, H.
The structure of (E)-biformene synthase provides insights into the biosynthesis of bacterial bicyclic labdane-related diterpenoids.
J.Struct.Biol., 207:29-39, 2019

PubMed Abstract: The labdane-related diterpenoids (LRDs) are a large group of natural products with a broad range of biological activities. They are synthesized through two consecutive reactions catalyzed by class II and I diterpene synthases (DTSs). The structural complexity of LRDs mainly depends on the catalytic activity of class I DTSs, which catalyze the formation of bicyclic to pentacyclic LRDs, using as a substrate the catalytic product of class II DTSs. To date, the structural and mechanistic details for the biosynthesis of bicyclic LRDs skeletons catalyzed by class I DTSs remain unclear. This work presents the first X-ray crystal structure of an (E)-biformene synthase, LrdC, from the soil bacterium Streptomyces sp. strain K155. LrdC was identified as a part of an LRD cluster of five genes and was found to be a class I DTS that catalyzes the Mg-dependent synthesis of bicyclic LRD (E)-biformene by the dephosphorylation and rearrangement of normal copalyl pyrophosphate (CPP). Structural analysis of LrdC coupled with docking studies suggests that Phe189 prevents cyclization beyond the bicyclic LRD product through a strong stabilization of the allylic carbocation intermediate, while Tyr317 functions as a general base catalyst to deprotonate the CPP substrate. Structural comparisons of LrdC with homology models of bacterial bicyclic LRD-forming enzymes (CldD, RmnD and SclSS), as well as with the crystallographic structure of bacterial tetracyclic LRD ent-kaurene synthase (BjKS), provide further structural insights into the biosynthesis of bacterial LRD natural products.

PubMed: 30981884
DOI: 10.1016/j.jsb.2019.04.010

実験手法

X-RAY DIFFRACTION (2.19 Å)