Conformations of nicotinamide adenine dinucleotide (NAD(+)) in various environments.
Enzymes bind NAD(+) in extended conformations and yet NAD(+) exists in aqueous solution as a compact, folded molecule. Thus, NAD(+) conformation is environment dependent. In an attempt to investigate the effects of environmental changes on the conformation of NAD(+), a series of molecular dynamics simulations in different solvents was performed. The solvents investigated (water, DMSO, methanol and chloroform) represented changes in relative permittivity and hydrophobic character. The simulations predicted folded conformations of NAD(+) to be more stable in water, DMSO and methanol. In contrast, extended conformations of NAD(+) were observed to be more stable in chloroform. Furthermore, the extended conformations observed in chloroform were similar to conformations of NAD(+) bound to enzymes. In particular, a large separation between the aromatic rings and a strong interaction between the pyrophosphate and nicotinamide groups were observed. The implications of these observations for the recognition of NAD(+) by enzymes is discussed. It is argued that a hydrophobic environment is important for stabilizing unfolded conformations of NAD(+).
Smith
P E
PE
Department of Biochemistry, Kansas State University, Manhattan, KS 66506-3702, USA.
Tanner
J J
JJ
D004121:Dimethyl Sulfoxide; D038181:FMN Reductase; D008958:Models, Molecular; D008968:Molecular Conformation; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012997:Solvents; D014867:Water
D011506:Proteins; D012997:Solvents; D014867:Water; D009243:NAD; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; D004121:Dimethyl Sulfoxide