Operations Research, Systems Engineering and Industrial Engineering Commons^™

Structure/Function Analyses Of Human Serum Paraoxonase (Hupon1) Mutants Designed From A Dfpase-Like Homology Model, David T. Yeung, Denis Josse, James D. Nicholson, Akhil Khanal, Christopher W. Mcandrew, Brian B. Bahnson, David E. Lenz, Douglas M. Cerasoli

US Army Research

Human serum paraoxonase (HuPON1) is a calcium-dependent enzyme that hydrolyzes esters, including organophosphates and lactones, and exhibits anti-atherogenic properties. A few amino acids have been shown to be essential for the enzyme’s arylesterase and organophosphatase activities. Until very recently, a three-dimensional model was not available for HuPON1, so functional roles have not been assigned to those residues. Based on sequence-structure alignment studies, we have folded the amino acid sequence of HuPON1 onto the sixfold β-propeller structure of squid diisopropylfluorophosphatase (DFPase). We tested the validity of this homology model by circular dichroism (CD) spectroscopy and site-directed mutagenesis. Consistent with predictions from …