Molecular Evolution and Genetic Engineering of Protein Domains Involving Aspartate Transcarbamoylase

AN INTRODUCTORY STATEMENT ...... . ... 194 PHYSIOLOGICAL ORGANIZATION OF PYRIMIDINE-ARGININE BIOSyNTHESIS 194 THE ENZYMATIC AND GENETIC ORGANIZATIONS INVOLVING ATCase....... 195 Appropriation of Regulatory Control in Bacteria . . ... ...... 196 The CA and CAD Early Enzyme Complexes . ... 199 THE MOLECULAR STRUCTURE OF THE ESCHERICHIA CaLl ATCase 200 The Structural T-R Transition........ .. . . . . . . . . ....... .. . . . .... . . . . . . . . . . . . . 200 Allosteric Control by Purine and Pyrimidine Nucleotide Effectors. . . . . .. . . . . . . . . . . . . . 202 Structural Characteristics of the Escherichia coli ATCase Model. . . . . . . . . . . . . . . . . . . . . . . 202 PRIMARY SEQUENCE OF ASPARTATE AND ORNITHINE TRANSCARBAMOYLASES 203 DNA and Deduced Amino Acid Sequence Comparisons 204 Conservation of Important Amino Acid Residues in Catalysis and Regulation. . . . . . . 205 Comparison of the ATCase and OTCases 207 FUNCTIONAL SWITCHING OF DISCRETE PROTEIN DOMAINS 208 Hybrid ATCases: Heterologous Exchange within the Enteric Bacteria 209 Chimeric ATCases: Heterologous Protein: Protein Fusions . . . . .. . . . . . . . . . . . . . . . ... . . . . 210 Formation of Hamster: Bacterial Chimeric ATCases ........ ......... 212 Chimeric ATCase: OTCase Proteins: Effective Switching of Catalytic Domains . . . . . 212 THE EVOLUTION OF DISCRETE PROTEIN FUNCTION........ .... 214