Minority Postdoctoral Research Fellowships in Biological Sciences for FY 2000

Wade, Herschel V, San Francisco CA

Investigators

Abstract

This action funds an NSF Minority Postdoctoral Research Fellowship in Biological Sciences for FY 2000. The research and training plan is in the area of biophysics and is entitled "Protein Engineering of a Model Protein." This study uses a synthetic diiron-oxo protein (DF) as a model for the class of metalloproteins that performs a variety of functions in living systems including dioxygen transport, conversion of ribonucleotides to deoxyribonucleotides, desaturation of fatty acids, and the solubilization and storage of iron. DF has been designed to serve as a minimal model of diiron-oxo proteins and has been shown to contain a metal center that is very similar to the diiron-oxo proteins. The model is interesting because the dinuclear metal centers in all diiron-oxo proteins contain many common structural features, but at the same time contain subtle differences that give rise to different activities. This makes the diiron-oxo system attractive for studying how protein environments can influence active site functions. This projects seeks to refine the first generation DF system into one that is amenable for engineering and designing efforts and for studying diiron-oxo protein function by (1) developing an efficient synthesis of DF which would offer a quick way to generate large numbers of DF variants and (2) by investigating the determinants for the function and structure of the center by systematically altering the atoms near the active site. Completing these goals will guide efforts towards designing pre-defined functions into the diiron-oxo centers.