8RON

Crystal structure of human FAD synthase, isoform 2

Summary for 8RON

• Entry DOI: 10.2210/pdb8ron/pdb
• Related: 8ROM
• Descriptor: Isoform 2 of FAD synthase (1 entity in total)
• Functional Keywords: human fad synthase, fad synthesis, fad hydrolysis, bifunctional protein, flavoprotein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 213526.12

Authors

Leo, G.,Capaldi, S. (deposition date: 2024-01-11, release date: 2024-04-10, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)