Biomimetic Modeling of Ni-ARD’s Active Site with Zinc and Nickel Metal Complexes

Presentation Author(s) Information

Morgan Ownbey, Georgia College and State University

Abstract

The acireductone dioxygenase (ARD) metalloenzymes regulates the formation of the polyamine biosynthesis inhibitor methylthioadenosine through the methionine salvage pathway, a biosynthetic pathway in plants and prokaryotes. The ARD protein incorporates nickel or iron depending on bioavailability. The Fe-ARD and Ni-ARD demonstrate unique structure-function relationship dependent solely on the metal bound. Both metal congeners share identical amino acid residues yet when Fe2+is incorporated into the metal center the catalytic activity change causes an off-pathway shunt. Dr. Santiago Toledo of Texas Lutheran University developed a family of biomimetic models of the ARD metalloenzymes, [NiII(OMe2(6-H-DPPN))], [ZnII(OMe2(6-HDPPN))], [ZnII(OPh(6-H-DPPN))] and [ZnII(OPh(6-HDPEN))], that approximates nickel and zinc coordination at the active site. Density Functional (DFT) computational investigations have been performed and theoretical molecules been shown to be identical in geometry to the experimental data which help provide insight to the metal dependence of this system.

Session Name:

Chemistry I

Start Date

10-4-2015 9:00 AM

End Date

10-4-2015 10:00 AM

Location

HSB 209

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Biomimetic Modeling of Ni-ARD’s Active Site with Zinc and Nickel Metal Complexes

HSB 209

The acireductone dioxygenase (ARD) metalloenzymes regulates the formation of the polyamine biosynthesis inhibitor methylthioadenosine through the methionine salvage pathway, a biosynthetic pathway in plants and prokaryotes. The ARD protein incorporates nickel or iron depending on bioavailability. The Fe-ARD and Ni-ARD demonstrate unique structure-function relationship dependent solely on the metal bound. Both metal congeners share identical amino acid residues yet when Fe2+is incorporated into the metal center the catalytic activity change causes an off-pathway shunt. Dr. Santiago Toledo of Texas Lutheran University developed a family of biomimetic models of the ARD metalloenzymes, [NiII(OMe2(6-H-DPPN))], [ZnII(OMe2(6-HDPPN))], [ZnII(OPh(6-H-DPPN))] and [ZnII(OPh(6-HDPEN))], that approximates nickel and zinc coordination at the active site. Density Functional (DFT) computational investigations have been performed and theoretical molecules been shown to be identical in geometry to the experimental data which help provide insight to the metal dependence of this system.