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Goodin Lab Research Themes
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Metalloenzyme Engineering One of the greatest challenges in the design of protein based catalysts is the simultaneous introduction of specificity and catalysis into the structure. Our research is focused on the structural re-engineering of enzymes to develop novel catalysts that are capable of oxidizing specific substrates. Our experimental approach involves the integrated use of multidisciplinary techniques including molecular modeling, protein engineering, x-ray crystallography, electron paramagnetic resonance, electrochemistry, calorimetry and kinetics. Engineered enzymes may have practical utility as bio-sensors, reagents for stereospecific chemical transformations and bio-remediation. More generally, our research may contribute to the understanding of metalloenzyme function, molecular recognition and drug design. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
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Enzyme Function We have a long standing interest in the structural and biophysical characterizationof a class of oxidative heme enzymes typified by the peroxidases and mono-oxygenases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
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Enzyme Engineering Our laboratory is developing methods for directed evolution of enzymes with novel function. The goal is to gain sufficient control over substrate-enzyme interactions and the subsequent oxidative chemistry catalyzed by hypervalent heme cofactors to allow directed evolution of catalysts capable of regio- and stereo-specific oxidation of a given target substrate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
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Molecular Wires We are working closely with the laboratory of H.B. Gray at the California Institute of Technology on developing the use of synthetic molecular wires to probe the active site and function of P450cam and nitric oxide synthase (NOS). These wires, consisting of substrate analogs tethered to a reporter or sensitizer, are designed to bind specifically to the active site channel of a given enzyme. Wires specific for the substrate or cofactor binding sites of a given enzyme will be useful tools for inhibitor discovery, photo-triggered enzyme turnover, and molecular evolution strategies. |
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