8QNB

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

Summary for 8QNB

• Entry DOI: 10.2210/pdb8qnb/pdb
• Descriptor: L-galactono-1,4-lactone dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, L-galactono-1,4-lactone, ... (4 entities in total)
• Functional Keywords: flavoprotein, oxidoreductases, anestral enzyme
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 58218.66

Authors

Boverio, A.,Mattevi, A. (deposition date: 2023-09-26, release date: 2024-05-01, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)