Still looking for the Ivory Tower.
Following graduate training, which was disrupted by my changing schools and serving in the Navy in World War II, I arrived in Berkeley in 1948 as an instructor in the Biochemistry Department. Despite numerous academic reorganizations and a host of struggles over the University-imposed Loyalty Oath, dismissal of a faculty member because of political affiliations, free speech for students, and my resistance to mandatory retirement, I survived with the help of great graduate students, postdoctoral fellows, undergraduates, superb research assistants, and a supportive wife. Studies on structure of tobacco mosaic virus led to our investigating an ultracentrifuge anomaly and the construction of a synthetic boundary cell. In turn, this resulted in about 15 years of research on the ultracentrifuge and its application to the study of biological macromolecules. Among the latter, the discovery of large ribonucleoprotein complexes, now known as ribosomes, and chromatophores in photosynthetic microorganisms attracted the most attention. But it was the development of the photoelectric absorption optical system and the incorporation of the Rayleigh interferometer onto the ultracentrifuge that had the greatest impact on our further research. These tools, when applied to our initial research on E. coli aspartate transcarbamoylase (ATCase), led to the discovery of distinct subunits for catalysis and regulation and the global conformational change in the enzyme associated with its role in regulation. For almost 35 years we have been using the techniques of protein chemistry and molecular biology in studies of structural and conformational changes in the enzyme, the genes encoding the different polypeptides, subunit interactions, and assembly of the enzyme from six catalytic and six regulatory chains. Hybrids constructed from inactive mutants were used to demonstrate shared active sites requiring the joint participation of amino acid residues from adjoining polypeptide chains. ATCase is still being studied as a model for understanding allostery as a regulatory mechanism. Circularly permuted polypeptide chains are being used to study the folding and assembly pathways, and the recently determined crystal structure of the active nonallosteric catalytic subunit has led to new questions regarding the activated form of ATCase.
Schachman
H K
HK
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3206, USA. schach@socrates.berkeley.edu
D001221:Aspartate Carbamoyltransferase / Q000235:genetics / Q000266:history; D001671:Biochemistry / Q000266:history*; D002140:California; D004926:Escherichia coli / Q000201:enzymology; D049673:History, 20th Century; D009316:National Institutes of Health (U.S.) / Q000266:history; D014027:Tobacco Mosaic Virus; D014461:Ultracentrifugation / Q000266:history; D014481:United States
D001221:Aspartate Carbamoyltransferase