Acireductone dioxygenase (ARD) is a metalloenzyme that plays a role in the ubiquitous methionine salvage pathway (MSP) across plants, animals, and bacteria. ARD catalyzes the penultimate step in the MSP and plays a role in regulation of polyamines, carbon monoxide, and the essential amino acid methionine. Because of this regulatory role, ARD has been linked to tumor formation, carcinogenesis, and hepatitis C, making it an enzyme of particular interest. Furthermore, ARD also performs dual chemistry based solely on the metal ion bound to its active site, leading to both on-pathway and off-pathway reactions that result in different products. The off-pathway reaction is of note due to the production of carbon monoxide, a known anti-apoptotic cell signaling molecule. While in bacteria, the off-pathway reaction is performed by Ni-ARD, it is known that Mn and Co bound ARD are capable of performing the off-pathway reaction in mammalian systems. In order to investigate the dual chemistry of ARD and elucidate the structure-function relationship of a human relevant metal in ARD specifically, a small molecular manganese complex was synthesized using a pyridine based, Schiff-base, N4O chelating ligand. Characterization of this complex and its derivatives will be presented. Preliminary reactivity studies with the resulting Mn(II) complex when exposed to oxygen and in the presence of substrate analogues will be discussed. This oxidative chemistry potentially holds biological implications for understanding the mechanism of Mn-ARD, as well as other important Mn containing enzymes like oxalate oxidase, quercetin dioxygenase, and manganese superoxide dismutase.

Synthesis and oxidative reactivity of a manganese(II) active site model of the mammalian enzyme manganese acireductone dioxygenase (Mn-ARD)

ACS Spring Meeting 2021

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