5EX9

Structure of P450 StaF from glycopeptide antibiotic A47934 biosynthesis; glycerol cryo

5EX9 の概要

• エントリーDOI: 10.2210/pdb5ex9/pdb
• 関連するPDBエントリー: 5EX8
• 分子名称: Cytochrome P450, PROTOPORPHYRIN IX CONTAINING FE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: cytochrome p450, monooxygenase, phenolic coupling, glycopeptide antibiotic biosynthesis, oxidoreductase
• 由来する生物種: Streptomyces toyocaensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48690.84

構造登録者

Cryle, M.J.,Ulrich, V. (登録日: 2015-11-23, 公開日: 2017-01-11, 最終更新日: 2024-01-10)

主引用文献

Ulrich, V.,Brieke, C.,Cryle, M.J.
Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934.
Beilstein J Org Chem, 12:2849-2864, 2016

PubMed Abstract: The chemical complexity and biological activity of the glycopeptide antibiotics (GPAs) stems from their unique crosslinked structure, which is generated by the actions of cytochrome P450 (Oxy) enzymes that affect the crosslinking of aromatic side chains of amino acid residues contained within the GPA heptapeptide precursor. Given the crucial role peptide cyclisation plays in GPA activity, the characterisation of this process is of great importance in understanding the biosynthesis of these important antibiotics. Here, we report the cyclisation activity and crystal structure of StaF, the D--E ring forming Oxy enzyme from A47934 biosynthesis. Our results show that the specificity of StaF is reduced when compared to Oxy enzymes catalysing C--D ring formation and that this activity relies on interactions with the non-ribosomal peptide synthetase via the X-domain. Despite the interaction of StaF with the A47934 X-domain being weaker than for the preceding Oxy enzyme StaH, StaF retains higher levels of in vitro activity: we postulate that this is due to the ability of the StaF/X-domain complex to allow substrate reorganisation after initial complex formation has occurred. These results highlight the importance of testing different peptide/protein carrier constructs for in vitro GPA cyclisation assays and show that different Oxy homologues can display significantly different catalytic propensities despite their overall similarities.

PubMed: 28144358
DOI: 10.3762/bjoc.12.284

実験手法

X-RAY DIFFRACTION (2.2 Å)