7CPY

Lovastatin nonaketide synthase with LovC

7CPY の概要

• エントリーDOI: 10.2210/pdb7cpy/pdb
• EMDBエントリー: 30435
• 分子名称: Lovastatin nonaketide synthase, enoyl reductase component lovC, Lovastatin nonaketide synthase, polyketide synthase component, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: polyketide synthase, biosynthetic protein
• 由来する生物種: Aspergillus terreus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 755625.90

構造登録者

Wang, J.,Wang, Z. (登録日: 2020-08-08, 公開日: 2021-01-13, 最終更新日: 2024-05-29)

主引用文献

Wang, J.,Liang, J.,Chen, L.,Zhang, W.,Kong, L.,Peng, C.,Su, C.,Tang, Y.,Deng, Z.,Wang, Z.
Structural basis for the biosynthesis of lovastatin.
Nat Commun, 12:867-867, 2021

PubMed Abstract: Statins are effective cholesterol-lowering drugs. Lovastatin, one of the precursors of statins, is formed from dihydromonacolin L (DML), which is synthesized by lovastatin nonaketide synthase (LovB), with the assistance of a separate trans-acting enoyl reductase (LovC). A full DML synthesis comprises 8 polyketide synthetic cycles with about 35 steps. The assembling of the LovB-LovC complex, and the structural basis for the iterative and yet permutative functions of the megasynthase have remained a mystery. Here, we present the cryo-EM structures of the LovB-LovC complex at 3.60 Å and the core LovB at 2.91 Å resolution. The domain organization of LovB is an X-shaped face-to-face dimer containing eight connected domains. The binding of LovC laterally to the malonyl-acetyl transferase domain allows the completion of a L-shaped catalytic chamber consisting of six active domains. This architecture and the structural details of the megasynthase provide the basis for the processing of the intermediates by the individual catalytic domains. The detailed architectural model provides structural insights that may enable the re-engineering of the megasynthase for the generation of new statins.

PubMed: 33558520
DOI: 10.1038/s41467-021-21174-8

実験手法

ELECTRON MICROSCOPY (3.6 Å)