Rutter, William

How would substrate preference be changed if the glycine residues in trypsin at positions 216 and 226 were changed to alanine rather than to the more bulky valine and threonine groups that are present in elastase This question was addressed by the groups of Charles Cralk, William Rutter, and Robert Fletterick in San Francisco, who have made and studied three such trypsin mutants one in which Ala is substituted for Gly at 216, one in which the same substitution is made at Gly 226, and a third containing both substitutions. 

Until recently, the catalytic role of Asp ° in trypsin and the other serine proteases had been surmised on the basis of its proximity to His in structures obtained from X-ray diffraction studies, but it had never been demonstrated with certainty in physical or chemical studies. As can be seen in Figure 16.17, Asp ° is buried at the active site and is normally inaccessible to chemical modifying reagents. In 1987, however, Charles Craik, William Rutter, and their colleagues used site-directed mutagenesis (see Chapter 13) to prepare a mutant trypsin with an asparagine in place of Asp °. This mutant trypsin possessed a hydrolytic activity with ester substrates only 1/10,000 that of native trypsin, demonstrating that Asp ° is indeed essential for catalysis and that its ability to immobilize and orient His is crucial to the function of the catalytic triad. 

William J. Rutter s laboratory al UCSF cloned a coal protein nf the vims that causes hepatitis, B. 

Caro-Beth Stewart and William J. Rutter, unpublished results (1990). 

William Rutter, the head of its Department of Biochemistry and Biophysics. As a result of their cooperative efforts and those of Benjamin Hall of the University of Washington, they were able to produce the necessary protein antigen. 

What would be preferable is a facility where early proof-of-concept experiments can be carried out with minimal commitments on infrastructure, taking advantage of shared resources like lab equipment, facilities, and analytical services. In fact, such incubators do exist today. Organizations like Synergenics, whose Chairman is Dr William Rutter, co-founder of Chiron and the San Jose Biocenter, provide start-up companies with not only facilities and shared capital equipment, but expertise in a variety of science (e.g. bioinformatics) as well as business issues. Another advantage they provide in bringing together a variety of start-ups is an atmosphere that may make the cross-pollination of ideas possible. 

Chiron Corp., Emeryville, California, founded in 1978 by William J. Rutter, pursued, unlike other start-ups, a wide menu of pharmaceuticals, including vaccines, diagnostics, and therapeutics. Hepatitis Delta (HDV) was cloned and characterized in Michael Houghtons laboratory in 1986 and in 1989 also Hepatitis C virus (HCV) [72, 83]. This latter along with PCR-based diagnostics allowed much-improved (1000-fold increased sensitivity also for HIV) safety for products still derived from blood serum, for example, for serum albumen used to stabilize other rDNA products used intravenously. 

Harwood, J.L., Abulnaja, A.O., Barrett, P.B., Herbert, D., Rutter, A.J. and Williams, M. In Cherif, A., Miled-Daoud, D.B., Marzouk, B., Smaoui, A. and Zarrouk, M., editors. Metabolism, Structure and Utilization of Plant Lipids. Tunis Centre National Pedagogique, 1992 319-326. 

Harwood J.L., Abulnaja K.O, Barrett P.B., Herbert D., Rutter A.J. and Williams M. Changes in lipid Metabolism caused by Environmental Factors.In "Metabolism, structure and Utilization of plant lipids". Ed. A. Cherif, D. Ben Miled, B. Marzouk, A. Smaoui and M. Zarrouk -CNP. Tunisia, 1992. 319-321. 

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