title: The transient catalytically competent coenzyme allocation into the active site of Anabaena ferredoxin NADP+ -reductase.
abstract: Ferredoxin-NADP(+) reductase (FNR) catalyses the electron transfer from ferredoxin to NADP(+) via its flavin FAD cofactor. A molecular dynamics theoretical approach is applied here to visualise the transient catalytically competent interaction of Anabaena FNR with its coenzyme, NADP(+). The particular role of some of the residues identified as key in binding and accommodating the 2'P-AMP moiety of the coenzyme is confirmed in molecular terms. Simulations also indicate that the architecture of the active site precisely contributes to the orientation of the N5 of the FAD isoalloxazine ring and the C4 of the coenzyme nicotinamide ring in the conformation of the catalytically competent hydride transfer complex and, therefore, contributes to the efficiency of the process. In particular, the side chain of the C-terminal Y303 in Anabaena FNR appears key to providing the optimum geometry by reducing the stacking probability between the isoalloxazine and nicotinamide rings, thus providing the required co-linearity and distance among the N5 of the flavin cofactor, the C4 of the coenzyme nicotinamide and the hydride that has to be transferred between them. All these factors are highly related to the reaction efficiency, mechanism and reversibility of the process.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias and Institute of Biocomputation and Physics of Complex Systems, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Peregrina
authors.forename: Isaías
authors.initials: I
authors.lastname: Lans
authors.forename: Milagros
authors.initials: M
authors.lastname: Medina
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D019943:Amino Acid Substitution; D017033:Anabaena / Q000201:enzymology*; D055162:Biocatalysis; D020134:Catalytic Domain; D003067:Coenzymes / Q000378:metabolism*; D005287:Ferredoxin-NADP Reductase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005415:Flavins / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009536:Niacinamide / Q000378:metabolism; D013997:Time Factors
chemical_list: D003067:Coenzymes; D005415:Flavins; D009536:Niacinamide; D000249:Adenosine Monophosphate; D005287:Ferredoxin-NADP Reductase