Magnetic Circular Dichroism Study of Dimetallic Hydrolase Enzymes, Poster 19

Recently, the use of hydrolase enzymes that contain dimetallic active sites has proven to be an important field of research in bioinorganic chemistry. The three enzymes, organophosphate hydrolase (OPH), ketol-acid... [ view full abstract ]

Recently, the use of hydrolase enzymes that contain dimetallic active sites has proven to be an important field of research in bioinorganic chemistry. The three enzymes, organophosphate hydrolase (OPH), ketol-acid reductoisomerase (KARI), and methionine aminopeptidase (MetAP), are studied with the purpose of better understanding their mechanisms. These enzymes have significant practical applications including bioremediation of pesticides and chemical weapons and potential antibiotic and antiangiogenesis drug candidates developed from enzyme inhibitors. Analysis of these three enzymes through variable temperature variable field magnetic circular dichroism (VTVH MCD) provides a qualitative assessment of the coordination number of the metals in the active site and reveals other important mechanistic and structural information. Parameters, such as the magnetic exchange coupling constant, were then fitted to the data to further assess mechanistic properties. Results suggest OPH and MetAP are composed of a five and a six-coordinate metal active sites while interestingly, the two KARI enzymes studied (OZA and TB) have different coordination numbers. The insights achieved into the mechanisms of these widely varied enzymes will allow for future developments to maximize functionality, with applications in bioremediation and drug development.