Noncovalent minimal assembly of exogenous histamine with hemin cofactor as a peroxidase-mimicking cooperative catalyst

• DOI: 10.1016/j.isci.2022.105257
• Publication Date: 2022-10-02T14:03:11Z
• Authors: Byunghwa Kang; Gyuri Park; Seong Hun Kim; Donghwa Lee; Seung Soo Oh
• Keywords: Hemin; Horseradish peroxidase; Non-covalent interactions; Imidazole

By mimicking the synergistic interplay of primary and secondary coordination spheres within native peroxidases, we demonstrate a scaffold-free, yet highly effective molecular-level cooperation between an iron(III)-containing hemin cofactor and exogenous histamine in accelerating a peroxidase-like reaction. Density functional theory computations predict that, among structurally similar molecules, the histamine is the most interactive partner of hemin to elicit a spontaneous peroxidation by electrostatically attracting the proton of hydrogen peroxide to its own imidazole and thermodynamically stabilizing a transition-state intermediate. Although the molecular weight of hemin-histamine pair is 763, 1.7% of the horseradish peroxidase, cooperative catalysis of two natural molecules exhibits 17.3 times greater catalytic efficiency (17.93 M-1s-1) and 57.8 times larger specific activity (36.45 μmol/min·mg) than the hemin alone (1.04 M-1s-1 and 0.63 μmol/min·mg). Despite no scaffold or covalent linkage, the self-assembly with hemin is highly histamine-specific in complex environments, leading rapid color changes by substrate oxidation within 10 s.