Jeffrey E. Flatgaard

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Glutathione-S-transferase (GST) isozyme-selective inhibitors were designed by an empirically guided strategy. In the first phase, literature data were used to select C-terminal modifications which generated maximum variation in the catalytic efficiency (Vmax/Km) for glutathione (GSH) analogs used as substrates with different rat GSTs. Also, on the basis of(More)
The filamentous ascomycete Aspergillus awamori secretes large amounts of glucoamylase upon growth in medium containing starch, glucose, or a variety of hexose sugars and sugar polymers. We examined the mechanism of this carbon source-dependent regulation of glucoamylase accumulation and found a several hundredfold increase in glucoamylase mRNA in cells(More)
A systematically diversified set of peptide analogs of the reaction product of glutathione with an electrophilic substrate have been tested as isozyme-specific inhibitors of human glutathione-S-transferase (GST). The potency of the best of the inhibitors is in the 0.5 to 20 micromolar range, with kinetics indicative of competitive inhibition with(More)
Unusual quaternary constraint in the regulatory enzyme, aspartate transcarbamylase (aspartate carbamoyltransferase or carbamoylphosphate:L-aspartate carbamoyltransferase, EC from Escherichia coli, was demonstrated with a hybrid composed of one inactive "catalytic" subunit from a mutant strain and one active catalytic subunit and three regulatory(More)
Using a combination of Epstein-Barr virus transformation and cell fusion to a mouse/human heteromyeloma cell line, we have generated a human monoclonal antibody, D234, that recognizes cross-reactive determinants on the lipopoly-saccharides (LPS) of Gram-negative bacteria. Direct binding to a series of rough mutant LPSs and smooth LPSs demonstrates the broad(More)
Two active mutants of aspartate transcarbamoylase from Escherichia coli have been purified from strains which produce large quantities of enzyme. Each enzyme was isolated from a different spontaneous revertant of a pyrimidine auxotrophic strain produced by mutagenesis with nitrogen mustard. Both enzymes exhibit allosteric properties with one having(More)
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