3T8E

Crystal structure of CerJ from Streptomyces tendae soaked with CerviK

3T8E の概要

• エントリーDOI: 10.2210/pdb3t8e/pdb
• 関連するPDBエントリー: 3S3L 3T5Y 3T6S
• 分子名称: CerJ, ACETATE ION (3 entities in total)
• 機能のキーワード: thiloase superfamily, fabh-like fold, o-malonyl transferase, transferase
• 由来する生物種: Streptomyces tendae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75326.49

構造登録者

Zocher, G.,Bretschneider, T.,Hertweck, C.,Stehle, T. (登録日: 2011-08-01, 公開日: 2011-12-21, 最終更新日: 2024-11-20)

主引用文献

Bretschneider, T.,Zocher, G.,Unger, M.,Scherlach, K.,Stehle, T.,Hertweck, C.
A ketosynthase homolog uses malonyl units to form esters in cervimycin biosynthesis.
Nat.Chem.Biol., 8:154-161, 2011

PubMed Abstract: Ketosynthases produce the carbon backbones of a vast number of biologically active polyketides by catalyzing Claisen condensations of activated acyl and malonyl building blocks. Here we report that a ketosynthase homolog from Streptomyces tendae, CerJ, unexpectedly forms malonyl esters during the biosynthesis of cervimycin, a glycoside antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). Deletion of cerJ yielded a substantially more active cervimycin variant lacking the malonyl side chain, and in vitro biotransformations revealed that CerJ is capable of transferring malonyl, methylmalonyl and dimethylmalonyl units onto the glycoside. According to phylogenetic analyses and elucidation of the crystal structure, CerJ is functionally and structurally positioned between the ketosynthase catalyzing Claisen condensations and acyl-ACP shuttles, and it features a noncanonical catalytic triad. Site-directed mutagenesis and structures of CerJ in complex with substrates not only allowed us to establish a model for the reaction mechanism but also provided insights into the evolution of this important subclass of the thiolase superfamily.

PubMed: 22179067
DOI: 10.1038/nchembio.746

実験手法

X-RAY DIFFRACTION (2.1 Å)