7UWR

KSQ+AT from first module of the pikromycin synthase

7UWR の概要

• エントリーDOI: 10.2210/pdb7uwr/pdb
• EMDBエントリー: 26839
• 分子名称: Narbonolide/10-deoxymethynolide synthase PikA1, modules 1 and 2 (2 entities in total)
• 機能のキーワード: ketosynthase-like, acyltransferase, decarboxylation, biosynthetic protein
• 由来する生物種: Streptomyces venezuelae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 183595.80

構造登録者

Keatinge-Clay, A.T.,Dickinson, M.S.,Miyazawa, T.,McCool, R.S. (登録日: 2022-05-03, 公開日: 2022-06-08, 最終更新日: 2024-06-12)

主引用文献

Dickinson, M.S.,Miyazawa, T.,McCool, R.S.,Keatinge-Clay, A.T.
Priming enzymes from the pikromycin synthase reveal how assembly-line ketosynthases catalyze carbon-carbon chemistry.
Structure, 30:1331-, 2022

PubMed Abstract: The first domain of modular polyketide synthases (PKSs) is most commonly a ketosynthase (KS)-like enzyme, KS, that primes polyketide synthesis. Unlike downstream KSs that fuse α-carboxyacyl groups to growing polyketide chains, it performs an extension-decoupled decarboxylation of these groups to generate primer units. When Pik127, a model triketide synthase constructed from modules of the pikromycin synthase, was studied by cryoelectron microscopy (cryo-EM), the dimeric didomain comprised of KS and the neighboring methylmalonyl-selective acyltransferase (AT) dominated the class averages and yielded structures at 2.5- and 2.8-Å resolution, respectively. Comparisons with ketosynthases complexed with their substrates revealed the conformation of the (2S)-methylmalonyl-S-phosphopantetheinyl portion of KS and KS substrates prior to decarboxylation. Point mutants of Pik127 probed the roles of residues in the KS active site, while an AT-swapped version of Pik127 demonstrated that KS can also decarboxylate malonyl groups. Mechanisms for how KS and KS domains catalyze carbon-carbon chemistry are proposed.

PubMed: 35738283
DOI: 10.1016/j.str.2022.05.021

実験手法

ELECTRON MICROSCOPY (2.61 Å)