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Lerner and Schultz – making catalysts from antibodies


Subtilisin had exactly the same proton relay
Manfred Eigen Scientist
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There was another proteolytic enzyme from a micro-organism... from bacillus, subtilis, called subtilisin... the enzyme. It does about the same job as the pancreatic enzyme, the trypsin, chymotrypsin. But it turned out that it had no relationship to that enzyme, in other words it was an entirely different protein. The length of the polypeptide chain was different, the arrangement was very different. So there was... and if you make a... if you line up the two molecules you see they have no common similarities or so... they came about in evolution in quite different organisms. But they had to do the same job. And the surprising result was this subtilisin, being a completely different molecule, had exactly the same proton relay. Here, a serine, with its OH group, in between a histidine with its imidazole ring, and on the other hand the aspartate as a proton acceptor. So you see evolution, whenever it needed a certain function, realised it with quite different structures. That means in one case you were at that point in sequence space, and you don't have to go far to get your optimal enzyme, your chymotrypsin or your trypsin. In the other case you were at a very different point in sequence space and you got also the same optimal enzyme, the subtilisin, both utilising the same principle in nature.

Nobel Prize winning German biophysical chemist, Manfred Eigen (1927-2019), was best known for his work on fast chemical reactions and his development of ways to accurately measure these reactions down to the nearest billionth of a second. He published over 100 papers with topics ranging from hydrogen bridges of nucleic acids to the storage of information in the central nervous system.

Listeners: Ruthild Winkler-Oswatitch

Ruthild Winkler-Oswatitsch is the eldest daughter of the Austrian physicist Klaus Osatitsch, an internationally renowned expert in gas dynamics, and his wife Hedwig Oswatitsch-Klabinus. She was born in the German university town of Göttingen where her father worked at the Kaiser Wilhelm Institute of Aerodynamics under Ludwig Prandtl. After World War II she was educated in Stockholm, Sweden, where her father was then a research scientist and lecturer at the Royal Institute of Technology.

In 1961 Ruthild Winkler-Oswatitsch enrolled in Chemistry at the Technical University of Vienna where she received her PhD in 1969 with a dissertation on "Fast complex reactions of alkali ions with biological membrane carriers". The experimental work for her thesis was carried out at the Max Planck Institute for Physical Chemistry in Göttingen under Manfred Eigen.

From 1971 to the present Ruthild Winkler-Oswatitsch has been working as a research scientist at the Max Planck Institute in Göttingen in the Department of Chemical Kinetics which is headed by Manfred Eigen. Her interest was first focused on an application of relaxation techniques to the study of fast biological reactions. Thereafter, she engaged in theoretical studies on molecular evolution and developed game models for representing the underlying chemical proceses. Together with Manfred Eigen she wrote the widely noted book, "Laws of the Game" (Alfred A. Knopf Inc. 1981 and Princeton University Press, 1993). Her more recent studies were concerned with comparative sequence analysis of nucleic acids in order to find out the age of the genetic code and the time course of the early evolution of life. For the last decade she has been successfully establishing industrial applications in the field of evolutionary biotechnology.

Tags: subtilisin, proteolytic enzyme, pancreatic enzyme, trypsin, chymotrypsin, proton relay, serine, histidine, imidazole ring, aspartate, sequence space

Duration: 1 minute, 50 seconds

Date story recorded: July 1997

Date story went live: 24 January 2008