7YWK

Crystal structure of an engineered TycA variant, TycApPLA, in complex with AMP

7YWK の概要

• エントリーDOI: 10.2210/pdb7ywk/pdb
• 分子名称: Tyrocidine synthase 1, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ADENOSINE MONOPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: nonribosomal peptide synthetase, adenylation domain, depsipeptide, ligase
• 由来する生物種: Brevibacillus parabrevis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96501.51

構造登録者

Mittl, P.,Camus, A.,Truong, G.,Markert, G.,Hilvert, D. (登録日: 2022-02-14, 公開日: 2022-09-21, 最終更新日: 2024-01-31)

主引用文献

Camus, A.,Truong, G.,Mittl, P.R.E.,Markert, G.,Hilvert, D.
Reprogramming Nonribosomal Peptide Synthetases for Site-Specific Insertion of alpha-Hydroxy Acids.
J.Am.Chem.Soc., 144:17567-17575, 2022

PubMed Abstract: High-throughput engineering has the potential to revolutionize the customization of biosynthetic assembly lines for the sustainable production of pharmaceutically relevant natural product analogs. Here, we show that the substrate specificity of gatekeeper adenylation domains of nonribosomal peptide synthetases can be switched from an α-amino acid to an α-hydroxy acid in a single round of combinatorial mutagenesis and selection using yeast cell surface display. In addition to shedding light on how such proteins discriminate between amino and hydroxy groups, the remodeled domains function in a pathway context to produce α-hydroxy acid-containing linear peptides and cyclic depsipeptides with high efficiency. Site-specific replacement of backbone amines with oxygens by an engineered synthetase provides the means to probe and tune the activities of diverse peptide metabolites in a simple and predictable fashion.

PubMed: 36070491
DOI: 10.1021/jacs.2c07013

実験手法

X-RAY DIFFRACTION (1.39 Å)