5-Fluorolysine as alternative substrate of lysine 5,6-aminomutase: A computational study

Lysine 5,6-aminomutase (5,6-LAM) catalyzes the interconversion of D-lysine and 2,5-diaminohexanoic acid, and L-β-Lysine and 3,5-diaminohexanoic acid by using adenosylcobalamin (AdoCbl) and pyridoxal-5′-phosphate (PLP) as cofactors and follows a radical mechanism. Several radical intermediates, including substrate related radical (S), cyclic azacyclopropylcarbinyl radical (I), and product related radical (P) have been proposed. Although no radical intermediate could be detected in the reaction of natural substrates, a computational study proposed that reaction with 4-thialysine would result in detection of corresponding S, which was subsequently detected later in the reaction of 4-thialysine by EPR. In this work, we have calculated relative energies of the plausible intermediates in the reaction of 5-fluorolysine with 5,6-LAM. The results suggest that corresponding substrate related radical (5-FS) would be detected by EPR. Additionally, we have also calculated 19F hyperfine coupling constants (HFCCs) for 5-FS using B3LYP and MP2 methods in conjunction with various basis sets. This inventory of 19F HFCCs would help to choose the appropriate level of theory to predict the 19F HFCCs for this kind of systems for comparing with the experimental values, whenever available from EPR and 19F ENDOR spectroscopy.