| Structural highlights
Disease
FAD1_HUMAN Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type;Multiple acyl-CoA dehydrogenase deficiency, mild type. The disease is caused by variants affecting the gene represented in this entry.
Function
FAD1_HUMAN Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme.[1] [2]
Publication Abstract from PubMed
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.
Structural insights into the bifunctional enzyme human FAD synthase.,Leo G, Leone P, Ataie Kachoie E, Tolomeo M, Galluccio M, Indiveri C, Barile M, Capaldi S Structure. 2024 Jul 11;32(7):953-965.e5. doi: 10.1016/j.str.2024.04.006. Epub , 2024 Apr 29. PMID:38688286[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Brizio C, Galluccio M, Wait R, Torchetti EM, Bafunno V, Accardi R, Gianazza E, Indiveri C, Barile M. Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase. Biochem Biophys Res Commun. 2006 Jun 9;344(3):1008-16. PMID:16643857 doi:10.1016/j.bbrc.2006.04.003
- ↑ Olsen RKJ, Koňaříková E, Giancaspero TA, Mosegaard S, Boczonadi V, Mataković L, Veauville-Merllié A, Terrile C, Schwarzmayr T, Haack TB, Auranen M, Leone P, Galluccio M, Imbard A, Gutierrez-Rios P, Palmfeldt J, Graf E, Vianey-Saban C, Oppenheim M, Schiff M, Pichard S, Rigal O, Pyle A, Chinnery PF, Konstantopoulou V, Möslinger D, Feichtinger RG, Talim B, Topaloglu H, Coskun T, Gucer S, Botta A, Pegoraro E, Malena A, Vergani L, Mazzà D, Zollino M, Ghezzi D, Acquaviva C, Tyni T, Boneh A, Meitinger T, Strom TM, Gregersen N, Mayr JA, Horvath R, Barile M, Prokisch H. Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. Am J Hum Genet. 2016 Jun 2;98(6):1130-1145. PMID:27259049 doi:10.1016/j.ajhg.2016.04.006
- ↑ 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. 2024 Jul 11;32(7):953-965.e5. PMID:38688286 doi:10.1016/j.str.2024.04.006
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