2H7Y

Pikromycin Thioesterase with covalent affinity label

2H7Y の概要

• エントリーDOI: 10.2210/pdb2h7y/pdb
• 関連するPDBエントリー: 1MNA 2H7X
• 分子名称: Type I polyketide synthase PikAIV, SULFATE ION, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: thioesterase, alpha/beta hydrolase, hydrolase
• 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: 68432.70

構造登録者

Giraldes, J.W.,Akey, D.L.,Kittendorf, J.D.,Sherman, D.H.,Smith, J.S.,Fecik, R.A. (登録日: 2006-06-06, 公開日: 2006-09-19, 最終更新日: 2024-11-06)

主引用文献

Giraldes, J.W.,Akey, D.L.,Kittendorf, J.D.,Sherman, D.H.,Smith, J.S.,Fecik, R.A.
Structural and Mechanistic Insights of Polyketide Macrolactonization from Polyketide-based Affinity Labels
NAT.CHEM.BIOL., 2:531-536, 2006

PubMed Abstract: Polyketides are a diverse class of natural products having important clinical properties, including antibiotic, immunosuppressive and anticancer activities. They are biosynthesized by polyketide synthases (PKSs), which are modular, multienzyme complexes that sequentially condense simple carboxylic acid derivatives. The final reaction in many PKSs involves thioesterase-catalyzed cyclization of linear chain elongation intermediates. As the substrate in PKSs is presented by a tethered acyl carrier protein, introduction of substrate by diffusion is problematic, and no substrate-bound type I PKS domain structure has been reported so far. We describe the chemical synthesis of polyketide-based affinity labels that covalently modify the active site serine of excised pikromycin thioesterase from Streptomyces venezuelae. Crystal structures reported here of the affinity label-pikromycin thioesterase adducts provide important mechanistic insights. These results suggest that affinity labels can be valuable tools for understanding the mechanisms of individual steps within multifunctional PKSs and for directing rational engineering of PKS domains for combinatorial biosynthesis.

PubMed: 16969373
DOI: 10.1038/nchembio822

実験手法

X-RAY DIFFRACTION (2.1 Å)