Theoretical analyses of photoinduced electron transfer in medium chain acyl-CoA dehydrogenase: Electron transfer in the normal region

Medium chain acyl-CoA dehydrogenase (MCAD) binds flavin adenine dinucleotide (FAD) as cofactor, and catalyze α,β-dehydrogenation of fatty acid acyl-CoA conjugates as the first step of β-oxidation of fatty acids in mitochondria. The dynamic properties of geometrical factors as distances between isoalloxazine (Iso) and the aromatic amino acids of Trp and Tyr were studied by molecular dynamic (MD) simulation. The center-to-center distances (Rc) between Iso and aromatic amino acids were shortest in Tyr365 (0.99 nm) and then in Trp156 (1.00 nm), Tyr123 (1.29 nm), Tyr362 (1.42 nm). The Iso moiety was buried inside the protein, and surrounded by rigid and hydrophobic amino acids. The motions of the aromatic amino acids were suggested to be cooperative and synchronized with each other at some places in the protein. H-bonds were formed between Iso and Tyr123, Val125, Thr126 and Thr158. Photoinduced electron transfer (ET) from aromatic amino acids to the excited Iso (Iso*) was analysed from the reported ultrafast fluorescence dynamics of MCAD with Kakitani and Mataga (KM) theory. The ET rate was fastest from Trp156, and then from Tyr365, Trp47, Tyr302 and Trp165 in this order. Physical constants contained in KM theory were determined by a best-fit procedure between the observed and calculated fluorescence decays. Most of those quantities were similar to those derived from other flavoproteins. The free energy related to electron affinity of Iso* ( G Iso 0 ) and dielectric constant (ɛ0) were, however, quite low compared to their mean values among four other flavoproteins, which was elucidated by the low polarity around Iso. The energy gap law of ET was examined and revealed that ET in MCAD takes place in the normal region.