Abstract 1650 Understanding metal preferences in homologous acetone carboxylases

This is the authors' abstract. We don't add key points for this paper.

Acetone can be utilized as a primary carbon source through carboxylation with acetone carboxylase. This carboxylation reaction is ATP- and metal-dependent where the reactants and ATP binding in the beta subunit lead to large conformational shifts as well as changes in coordination of the active site metal in the alpha subunit. Homologous acetone carboxylases share up to 70% of their primary sequence; however, acetone carboxylases can have different affinities of metal binding for catalysis. Acetone carboxylases from Xanthobacter autotrophicus and Aromatoleum aromaticum strictly utilize Mn(II) and Fe(II) in their respective active sites. The ability for acetone carboxylase from Xanthobacter autotrophicus to bind Mn(II) over Fe(II) is contrary to the Irving-Williams series of hierarchal metal binding, which predicts the stability of divalent first row transition metals as increasing across the row. There are no known chaperones for acetone carboxylase to assist with metal binding; therefore, the enzyme structure itself has specific affinity with the metal in the active site. Understanding the determinants that dictate metal affinity will provide fundamental knowledge of metal catalysis design and function. We will present progress on our understanding of the structure-function relationship between acetone carboxylase enzymes and metal binding affinity for reaction catalysis. This work was supported by the US DOE, Office of Science, Office of Basic Energy Sciences under award DE-SC0018143 to J.W.P., B.B., and J.L.D.