Professor of Chemistry, Biochemistry and Molecular Biology
email: jfkirsch@berkeley.edu
office: 529A Stanley
phone: 510.642.6368
lab: 523, 529 and 530 Stanley
lab phone: 510.642.7373
Research Interests
Biophysical Chemistry Enzymology — Site directed mutagenesis is used to explore enzyme mechanisms, protein/protein interactions, and protein structure and thermostability.
Research in Professor Kirsch's group is centered on several areas of biophysical chemistry and structural biology that are conveniently probed by a combination of chemical and molecular biological techniques. The topics include: the mechanisms of enzymatic catalysis, and of protein/protein recognition.
The enzymatic investigations are centered on pyridoxal phosphate dependent reactions. This coenzyme is derived from vitamin B6, and is an important component of many enzymes involved in amino acid metabolism. Our approach utilizes rational and evolutionary methods to design new specificity and reaction types into the framework of known enzymes. The newly designed or evolved enzymes are studied by the appropriate methods of mechanistic enzymology.
Protein/protein recognition is investigated by site directed mutagenesis of residues in crystallographically defined antigen antibody complexes. Double mutant cycles have led to a protocol that allows us to define the trajectories for protein docking; i.e. we can state which parts of a complex are formed rapidly and distinguish them from contact areas that anneal slowly. The range of application of what we call "high resolution epitope mapping" is being expanded with enzyme inhibitor complexes.
Students in the group have found that certain combinations of nonpolar amino acids at a critical hinge region of the protein greatly increase its thermal stability, and have combined six single thermostabilizing mutations to produce a hyperthermostable lysozyme. This modified enzyme is a platform for protein folding investigations.
Biography
Professor of Chemistry and of Biochemistry and Molecular Biology, born 1934; B.S. University of Michigan (1956); Ph.D. Biochemistry and Cytology, Rockefeller University (1961); Brandeis University Jane Coffin Childs Postdoctoral Fellow (1961-3); Weizmann Institute of Science Helen Hay Whitney Postdoctoral Fellow (1963-4); Max Planck Institute for Biophysical Chemistry Guggenheim Fellow (1971-2); Biocenter University of Basel Visiting Professor (1979-80); Member AAAS, American Chemical Society (Chair Biochemistry Division (1996-8)), American Society for Biochemistry and Molecular Biology.