6FSH

Crystal structure of hybrid P450 OxyBtei(BC/FGvan)

6FSH の概要

• エントリーDOI: 10.2210/pdb6fsh/pdb
• 分子名称: OxyB protein, PROTOPORPHYRIN IX CONTAINING FE, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: cytochrome p450, phenolic coupling enzyme, teicoplanin biosynthesis, oxidoreductase
• 由来する生物種: Actinoplanes teichomyceticus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 178651.16

構造登録者

Brieke, C.,Tarnawski, M.,Greule, A.,Cryle, M.J. (登録日: 2018-02-19, 公開日: 2018-05-23, 最終更新日: 2024-01-17)

主引用文献

Brieke, C.,Tarnawski, M.,Greule, A.,Cryle, M.J.
Investigating Cytochrome P450 specificity during glycopeptide antibiotic biosynthesis through a homologue hybridization approach.
J. Inorg. Biochem., 185:43-51, 2018

PubMed Abstract: Cytochrome P450 enzymes perform an impressive range of oxidation reactions against diverse substrate scaffolds whilst generally maintaining a conserved tertiary structure and active site chemistry. Within secondary metabolism, P450 enzymes play widespread and important roles in performing crucial modifications of precursor molecules, with one example of the importance of such reactions being found in the biosynthesis of the glycopeptide antibiotics (GPAs). In GPA biosynthesis P450s, known as Oxy enzymes, are key players in the cyclization of the linear GPA peptide precursor, which is a process that is both essential for their antibiotic activity and is the source of the synthetic challenge of these important antibiotics. In this work, we developed chimeric P450 enzymes from GPA biosynthesis based on two homologues from different GPA biosynthesis pathways - vancomycin and teicoplanin - as an approach to explore the divergent catalytic behavior of the two parental homologues. We could generate, crystalize and explore the activity of new hybrid P450 enzymes from GPA biosynthesis and show that the unusual in vitro behavior of the vancomycin OxyB homologue does not stem from the major regions of the P450 active site, and that additional regions in and around the P450 active site must contribute to the unusual properties of this P450 enzyme. Our results further show that it is possible to successfully transplant entire regions of secondary structure between such P450s and retain P450 expression and activity, which opens the door to use such targeted approaches to generate and explore novel biosynthetic P450 enzymes.

PubMed: 29751197
DOI: 10.1016/j.jinorgbio.2018.05.001

実験手法

X-RAY DIFFRACTION (2.5 Å)