TRANSITION STRUCTURE AND REACTIVE COMPLEXES FOR HYDRIDE TRANSFER IN AN ISOALLOXAZINE-NICOTINAMIDE COMPLEX - ON THE CATALYTIC MECHANISM OF GLUTATHIONE-REDUCTASE - AN AB-INITIO MO SCF STUDY
W. Diaz et al., TRANSITION STRUCTURE AND REACTIVE COMPLEXES FOR HYDRIDE TRANSFER IN AN ISOALLOXAZINE-NICOTINAMIDE COMPLEX - ON THE CATALYTIC MECHANISM OF GLUTATHIONE-REDUCTASE - AN AB-INITIO MO SCF STUDY, Chemical physics, 204(2-3), 1996, pp. 195-203
An analysis is presented of the catalytic mechanism of glutathione red
uctase based upon a theoretically characterized saddle point of index
one obtained for a model representing the active groups of the flavine
and nicotinamide adenine dinucleotide phosphate, namely, an isoalloxa
zine and nicotinamide rings, The isoalloxazine rings appears deformed
into a butterfly conformation in the saddle point of index one. The bu
tterfly conformation is retained along the path leading to a reduced i
soalloxazine (N5-H) forcing the transferred hydrogen to stick into the
nicotinamide binding site, this geometric feature suggests the existe
nce of a transposed hydride transfer path where the NS-proton goes bac
k to a lysine residue leaving the electrons on FAD. This mechanism is
discussed and proposed as an alternative catalytic pathway in glutathi
one reductase to the standard electron transfer one, These results hel
p to understand the riddle created by the changing kinetic behavior of
glutathione reductase when, for instance, 2,4,6-trinitro-benzene sulf
onate is used to study in vitro kinetics or when specific site directe
d mutagenesis is performed.