8ROM

Crystal structure of human FAD synthase PAPS domain in complex with FAD

8ROM の概要

• エントリーDOI: 10.2210/pdb8rom/pdb
• 分子名称: FAD synthase, FLAVIN-ADENINE DINUCLEOTIDE, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: human fad synthase, fad synthesis, fad hydrolysis, bifunctional protein, flavoprotein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23701.44

構造登録者

Leo, G.,Capaldi, S. (登録日: 2024-01-11, 公開日: 2024-04-10, 最終更新日: 2024-11-20)

主引用文献

Leo, G.,Leone, P.,Ataie Kachoie, E.,Tolomeo, M.,Galluccio, M.,Indiveri, C.,Barile, M.,Capaldi, S.
Structural insights into the bifunctional enzyme human FAD synthase.
Structure, 32:953-, 2024

PubMed Abstract: Human flavin adenine dinucleotide synthase (hFADS) is a bifunctional, multi-domain enzyme that exhibits both flavin mononucleotide adenylyltransferase and pyrophosphatase activities. Here we report the crystal structure of full-length hFADS2 and its C-terminal PAPS domain in complex with flavin adenine dinucleotide (FAD), and dissect the structural determinants underlying the contribution of each individual domain, within isoforms 1 and 2, to each of the two enzymatic activities. Structural and functional characterization performed on complete or truncated constructs confirmed that the C-terminal domain tightly binds FAD and catalyzes its synthesis, while the combination of the N-terminal molybdopterin-binding and KH domains is the minimal essential substructure required for the hydrolysis of FAD and other ADP-containing dinucleotides. hFADS2 associates in a stable C2-symmetric dimer, in which the packing of the KH domain of one protomer against the N-terminal domain of the other creates the adenosine-specific active site responsible for the hydrolytic activity.

PubMed: 38688286
DOI: 10.1016/j.str.2024.04.006

実験手法

X-RAY DIFFRACTION (1.69 Å)