MIMICKING THE SECONDARY SPHERE OF HOMOPROTOCATECHUATE DIOXYGENASE (HPCD) ENZYME ACTIVE SITE; A THEORETICAL STUDY

Abstract

Fe-HPCD is a non-heme extradiol enzyme that operates in the oxidative ring opening pathways of aromatic compounds.[1,2] Recent studies showed that the proton transfer to afford 3 or 4 from 0 (Figure 1) is assisted by an His200 residue that is lying in the secondary sphere of HPCD active site.[3,4] Thus, the main role of His200 is acting as a Bronsted base. Herein, we present a Density Functional Theory analysis of the energetics of a modified first coordination shell with the objective of mimicking the role of His200 by incorporation of various functional groups on one of the imidazole rings (Figure 1). The aim is to create a proton transfer agent that is adequate in terms of thermodynamic and kinetic parameters in comparison with the native protein environment. Figure 1 shows the reaction mechanism and possible functional groups capable to act as a proton shuttle.