6W0S

Crystal structure of substrate free cytochrome P450 NasF5053 from Streptomyces sp. NRRL F-5053

6W0S の概要

• エントリーDOI: 10.2210/pdb6w0s/pdb
• 分子名称: cytochrome P450-F5053, GLYCEROL, BROMIDE ION, ... (7 entities in total)
• 機能のキーワード: biosynthetic protein, cytochrome p450, cyclodipeptide, regio-selecitivty, stereo-selectivity, pyrroloindoline alkaloids, radical mediated reaction, f5053, streptomyces, oxidoreductase
• 由来する生物種: Streptomyces sp. NRRL F-5053
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88821.53

構造登録者

Luo, Z.,Jia, X.,Sun, C.,Qu, X.,Kobe, B. (登録日: 2020-03-02, 公開日: 2020-11-11, 最終更新日: 2023-10-11)

主引用文献

Sun, C.,Luo, Z.,Zhang, W.,Tian, W.,Peng, H.,Lin, Z.,Deng, Z.,Kobe, B.,Jia, X.,Qu, X.
Molecular basis of regio- and stereo-specificity in biosynthesis of bacterial heterodimeric diketopiperazines.
Nat Commun, 11:6251-6251, 2020

PubMed Abstract: Bacterial heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are a growing family of bioactive natural products. They are challenging to prepare by chemical routes due to the polycyclic and densely functionalized backbone. Through functional characterization and investigation, we herein identify a family of three related HTDKP-forming cytochrome P450s (NasbB, Nas and Nas) and reveal four critical residues (Qln65, Ala86, Ser284 and Val288) that control their regio- and stereo-selectivity to generate diverse dimeric DKP frameworks. Engineering these residues can alter the specificities of the enzymes to produce diverse frameworks. Determining the crystal structures (1.70-1.47 Å) of Nas (ligand-free and substrate-bound Nas and its Q65I-A86G and S284A-V288A mutants) and molecular dynamics simulation finally elucidate the specificity-conferring mechanism of these residues. Our results provide a clear molecular and mechanistic basis into this family of HTDKP-forming P450s, laying a solid foundation for rapid access to the molecular diversity of HTDKP frameworks through rational engineering of the P450s.

PubMed: 33288748
DOI: 10.1038/s41467-020-20022-5

実験手法

X-RAY DIFFRACTION (1.7 Å)