title: Theoretical investigation of the "CO in"-"CO out" isomerization in a [2Fe-2S] ferredoxin: free energy profiles and redox states.
abstract: This paper reports on extensive molecular dynamics simulations (about 40 ns in total) in both the reduced and the oxidized states of Ferredoxin from Cyanobacterium Anabaena PCC7119. These calculations have provided us with the free energy profile of the phi(47) backbone angle which controls the "CO in" to "CO out" transition of Cys46 in the reduced and oxidized Fd7119. Our main motivation has been to identify the time scales involved in the reduction of Fd and single out the amino acid residues crucially affecting the conformational change and, thus, electron transfer. The free energy profiles obtained in this study are relevant to electron transfers in the PSI/Fd7119 and Fd7119/FNR complexes. Our findings based on hydrated ferredoxin simulations are that activated processes are to occur in the protein during electron transfer to and from ferredoxin. The relative stability and the activation barrier of the "CO in" to "CO out" transition can be modulated by the distance between the Ser47 and the Glu94 residues. In our calculations, for short distances, the "CO in" state is favored in the reduced form, whereas for large distances, the "CO out" state becomes increasingly favored. Accordingly, conformational changes in Fd7119 when bound to PSI or FNR can have crucial effects on the kinetics of the electron transfer. Our simulations also show that the hydrogen bond between between Ser47(OG) and Cys46(O) is essential to lock in the "CO out" state. This finding explains why only the Ser47Thr Fd7119 mutant sustains electron transfer activity, as only residues serine and threonine can form a specific hydrogen bond with Cys46(O). Finally, our simulations predict that Phe65 has a large probability of being in close contact with the Cys46(O) at the top of the conformational free energy barrier. This carbonyl/phenyl ring interaction can then facilitate the de-localization of the Fd's electron toward the Pi orbitals of Phe65 aromatic ring which is thought to be crucial to the Fd7119/FNR electron transfer
authors.affiliation: Commissariat à l'Energie Atomique, DSV-DBJC-SBFM, Centre d'Etudes, Saclay, 91191 Gif-sur-Yvette Cedex, France.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pizzitutti
authors.forename: Pierre
authors.initials: P
authors.lastname: Sétif
authors.forename: Massimo
authors.initials: M
authors.lastname: Marchi
mesh_terms: D002248:Carbon Monoxide / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D000458:Cyanobacteria / Q000737:chemistry / Q000378:metabolism; D005288:Ferredoxins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D012996:Solutions; D013816:Thermodynamics
chemical_list: C081714:2Fe-2S ferredoxin; D005288:Ferredoxins; D012996:Solutions; D002248:Carbon Monoxide