Charge-Transfer Interactions of Flavoenzymes

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The charge-transfer (CT) interaction between flavoenzyme acyl-CoA dehydrogenase (ACD) and substrate analog, 3-thiaacyl-CoA, was investigated by the combination of the X-ray crystallography, the spectroscopy (13C-NMR and electronic absorption) and the theoretical treatments. Different from the substrate, the analog inhibits the hydride transfer process after the α-proton is abstracted in the active site of the enzyme. The density functional theory (DFT) calculations were applied to the simplest model constructed with lumiflavin and deprotonated ethylthioester of 3-thiabtanoic acid. The optimized structure of the model complex is quite similar to the alignments determined by the X-ray crystallography. And the simulations of the 13C chemical shifts and the electronic excitation energy of the model are coincident with the observed ones. The highest occupied molecular orbital (HOMO) of the complex revealed that the bonding orbital is generated between the S(3) atom of the analog and the N5 atom of the flavin ring. Mulliken population analysis evaluates the quantity of the charge transfer from anionic analog to oxidized flavin as to be -0.28 charges. The bonding orbital between the S(3) and N5 atoms is analogous to the hydride transfer process in the case of the redox reaction of a substrate; therefore 3-thiaacyl-CoA is regarded as a transition-state analog. The research on the CT interaction of ACD provided the validity of the DFT calculations to the flavoenzymes. Further researches are applicable to the entire process of the ACD reaction and the other flavoenzymes.