6CUV

Engineered Holo TrpB from Pyrococcus furiosus, PfTrpB7E6

6CUV の概要

• エントリーDOI: 10.2210/pdb6cuv/pdb
• 分子名称: Tryptophan synthase beta chain 1, SODIUM ION, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: internal aldimine, lyase
• 由来する生物種: Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 170735.14

構造登録者

Scheele, R.A.,Buller, A.R.,Boville, C.E.,Arnold, F.H. (登録日: 2018-03-26, 公開日: 2018-09-26, 最終更新日: 2023-11-15)

主引用文献

Boville, C.E.,Scheele, R.A.,Koch, P.,Brinkmann-Chen, S.,Buller, A.R.,Arnold, F.H.
Engineered Biosynthesis of beta-Alkyl Tryptophan Analogues.
Angew. Chem. Int. Ed. Engl., 57:14764-14768, 2018

PubMed Abstract: Noncanonical amino acids (ncAAs) with dual stereocenters at the α and β positions are valuable precursors to natural products and therapeutics. Despite the potential applications of such bioactive β-branched ncAAs, their availability is limited due to the inefficiency of the multistep methods used to prepare them. Herein we report a stereoselective biocatalytic synthesis of β-branched tryptophan analogues using an engineered variant of Pyrococcus furiosus tryptophan synthase (PfTrpB), PfTrpB . PfTrpB is the first biocatalyst to synthesize bulky β-branched tryptophan analogues in a single step, with demonstrated access to 27 ncAAs. The molecular basis for the efficient catalysis and broad substrate tolerance of PfTrpB was explored through X-ray crystallography and UV/Vis spectroscopy, which revealed that a combination of active-site and remote mutations increase the abundance and persistence of a key reactive intermediate. PfTrpB provides an operationally simple and environmentally benign platform for the preparation of β-branched tryptophan building blocks.

PubMed: 30215880
DOI: 10.1002/anie.201807998

実験手法

X-RAY DIFFRACTION (2.26 Å)