8QNB

Crystal structure of ancestral L-galactono-1,4-lactone dehydrogenase: in complex with L-galactono-1,4-lactone

8QNB の概要

• エントリーDOI: 10.2210/pdb8qnb/pdb
• 分子名称: L-galactono-1,4-lactone dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, L-galactono-1,4-lactone, ... (4 entities in total)
• 機能のキーワード: flavoprotein, oxidoreductases, anestral enzyme
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58218.66

構造登録者

Boverio, A.,Mattevi, A. (登録日: 2023-09-26, 公開日: 2024-05-01, 最終更新日: 2024-11-13)

主引用文献

Boverio, A.,Jamil, N.,Mannucci, B.,Mascotti, M.L.,Fraaije, M.W.,Mattevi, A.
Structure, mechanism, and evolution of the last step in vitamin C biosynthesis.
Nat Commun, 15:4158-4158, 2024

PubMed Abstract: Photosynthetic organisms, fungi, and animals comprise distinct pathways for vitamin C biosynthesis. Besides this diversity, the final biosynthetic step consistently involves an oxidation reaction carried out by the aldonolactone oxidoreductases. Here, we study the origin and evolution of the diversified activities and substrate preferences featured by these flavoenzymes using molecular phylogeny, kinetics, mutagenesis, and crystallographic experiments. We find clear evidence that they share a common ancestor. A flavin-interacting amino acid modulates the reactivity with the electron acceptors, including oxygen, and determines whether an enzyme functions as an oxidase or a dehydrogenase. We show that a few side chains in the catalytic cavity impart the reaction stereoselectivity. Ancestral sequence reconstruction outlines how these critical positions were affixed to specific amino acids along the evolution of the major eukaryotic clades. During Eukarya evolution, the aldonolactone oxidoreductases adapted to the varying metabolic demands while retaining their overarching vitamin C-generating function.

PubMed: 38755143
DOI: 10.1038/s41467-024-48410-1

実験手法

X-RAY DIFFRACTION (2.1 Å)