An Interest in Chemotaxis, Not Jeans: the Work of Daniel E. Koshland
Year: 2007
Type: article
Abstract: Evidence for Protein Kinase Activities in the Prokaryote Salmonella typhimurium (Wang, J. Y., and Koshland, D. E., Jr. (1978) J. Biol. Chem. 253, 7605–7608) Membrane Receptors for Aspartate and Serine in Bacterial Chemotaxis (Clarke, S., and Koshland, D. E., Jr. (1979) J. Biol. Chem. 254, 9695–9702) Daniel Edward Koshland, Jr. (1920–2007) was born in New York City. He was the son of Daniel E. Koshland, Sr., a banker who joined Levi Strauss & Co. in 1922 and moved his family west to San Francisco. Koshland Sr. eventually became vice president, president, and chairman of the board of the company, remaining with the clothing manufacturer for 57 years. Koshland Jr. developed an interest in science, however, not jeans. He decided to become a scientist in the eighth grade after reading Microbe Hunters, by Paul DeKruif, and Arrowsmith, by Sinclair Lewis. He recalled, “Being a scientist seemed highly desirable, so when I entered high school I enrolled in college preparatory courses and took all the math, physics, and chemistry I was allowed” (1Koshland Jr., D.E. How to get paid for having fun..Annu. Rev. Biochem. 1996; 65: 1-13Crossref PubMed Scopus (4) Google Scholar). After graduating from high school, Koshland enrolled at the University of California, Berkeley. He received his B.S. in chemistry in 1941 and accepted a job at the Shell Chemical Company in Martinez, California. When World War II started, he tried to enlist in the Navy but was told that with his 20/400 eyesight, he was legally blind as far as the Navy was concerned. However, shortly thereafter he received a call from Wendell Latimer, one of his former professors at Berkeley. Latimer explained that Glen Seaborg was recruiting scientists to work on the Manhattan Project at the University of Chicago. Although Koshland had no idea what the Manhattan Project was, he accepted the offer and a few weeks later he was on his way to Chicago. During his tenure with the Manhattan Project, Koshland's primary responsibilities involved purifying plutonium for the construction of the first plutonium-based fission bomb. When the war came to an end, Koshland decided to remain at the University of Chicago and earn a Ph.D. in biochemistry. Working with Frank Westheimer, he used radioactive carbon 14 to study the metabolism of glucose. He received his Ph.D. in 1949 and moved to Harvard University to do a postdoctoral fellowship with Paul Bartlett, focusing on enzymatic reactions. After completing his 2-year fellowship, Koshand began to look for a job. However, the job situation was very tight in the early 1950s, and Koshland's varied background in chemistry and biology didn't help. He finally accepted an appointment at the Brookhaven National Laboratory, and although he only planned to remain there for a year or two, he ended up staying at Brookhaven for 14 years, first as an associate biochemist, then a biochemist, and finally a senior biochemist. At Brookhaven, Koshland developed the “induced fit” theory of enzymatic action, a modification of Emil Fischer's “lock and key” model in which both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. Koshland proposed that some enzymes were in fact flexible and that the active site is continually reshaped by interactions with the substrate. He published the theory in the Proceedings of the National Academy of Sciences (2Koshland Jr., D.E. Application of a theory of enzyme specificity to protein synthesis..Proc. Natl. Acad. Sci. U. S. A. 1958; 44: 98-104Crossref PubMed Google Scholar). Koshland's theory, like many new theories, was met with skepticism. One referee wrote that “The Fischer Key-Lock theory has lasted 100 years and will not be overturned by speculation from an embryonic scientist” (1Koshland Jr., D.E. How to get paid for having fun..Annu. Rev. Biochem. 1996; 65: 1-13Crossref PubMed Scopus (4) Google Scholar). Koshland and his colleagues subsequently provided more evidence to support the theory, and it is now widely accepted as an explanation for the behavior of many enzymes. The induced fit theory later led Koshland, along with George Némethy and David Filmer, to put forward an enzymatic model to explain protein/enzyme cooperativity (3Koshland Jr., D.E. Nemethy G. Filmer D. Comparison of experimental binding data and theoretical models in proteins containing subunits..Biochemistry. 1966; 5: 365-385Crossref PubMed Scopus (2194) Google Scholar). Their Sequential Model proposed that ligand binding causes enzymatic subunits to go through conformational changes independently of one another. This differed from the Concerted Model proposed by Jacques Monod, Jeffries Wyman, and Jean-Pierre Changeux, which stated that enzyme subunits are connected in such a way that a conformational change in one subunit is necessarily conferred to all other subunits (4Monod J. Wyman J. Changeux J.P. On the nature of the allosteric transition: a plausible model..J. Mol. Biol. 1965; 12: 88-118Crossref PubMed Scopus (6130) Google Scholar). During his time at Brookhaven, Koshland also became interested in muscular contraction and used lobster as a source of muscle in his experiments. Because lobster muscle was essentially a pure ATPase, he was able to add an excess of H 182O to the muscle, let the H 182O exchange with the water in the muscle, let the reaction run in the intact lobster muscle, and then analyze the resulting ATP, ADP, and inorganic phosphate for 18O content. He submitted his manuscript to the Journal of Biological Chemistry (JBC) (5Koshland Jr., D.E. Clarke E. Mechanism of hydrolysis of adenosinetriphosphate catalyzed by lobster muscle..J. Biol. Chem. 1953; 205: 917-924Abstract Full Text PDF PubMed Google Scholar), and although it was accepted he later learned that Carl Cori, who reviewed the manuscript, commented that “some nutty, young scientist at Brookhaven National Laboratory has added a whole lobster tail to a solution and thinks he's studying an enzymatic reaction” (1Koshland Jr., D.E. How to get paid for having fun..Annu. Rev. Biochem. 1996; 65: 1-13Crossref PubMed Scopus (4) Google Scholar). In 1964, Koshland was offered an appointment in the Department of Biochemistry at the University of California at Berkeley. He assumed his new position as Professor of Biochemistry in 1965 and remained there until his death in 2007. He served as chair of the department between 1973 and 1978. In the 1970s, Koshland's interest turned to the mechanism by which cells “remember” situations and events. His experiments on bacterial chemotaxis led to important new understanding on how organisms develop short- and long-term memory. Although the first JBC Classic paper reprinted here is not a chemotaxis paper, it was the first demonstration of protein serine/threonine phosphorylation in bacteria. At that time, it was known that protein phosphorylation played a key role in the regulation of enzyme activity in many eukaryotic systems, but there was no proof that a prokaryotic protein kinase existed. Koshland and several others had shown that both prokaryotes and eukaryotes undergo reversible protein methylation, and he suspected that prokaryotic proteins also underwent phosphorylation. He and Jean Yin Jen Wang pulse-labeled cells from Samonella typhimurium cells with 32Pi and analyzed the cell contents by SDS-polyacrylamide gel electrophoresis and autoradiography. They found four proteins that were labeled with 32P, confirming that protein phosphorylation did occur in prokaryotes. These findings initiated a line of research that led to a structure-function analysis of tricarboxylic acid cycle/glyoxylate shunt regulation. The second JBC Classic reprinted here is the first paper to identify the two major chemotaxis receptors in Escherichia coli membranes, the serine and aspartate receptors (Tsr and Tar). In the paper, Koshland and Steven Clarke report that cell membranes contain at least 2500 serine receptors and 1200 aspartate receptors. They also found that mutants lacking the receptors have corresponding defects in taxis. This initiated a line of research in the Koshland lab that established these receptors as a paradigm for transmembrane signaling. In 1984, Koshland was offered the position of editor-in-chief at Science magazine. He held the post for 10 years, during which he was best known for his incisive and witty editorials. This was most evident in the character he created, “Dr. Noitall,” who was intended to represent the many scientists who took narrow, overly simplistic views of important issues. As editor of Science Koshland also streamlined the system of reviewing manuscripts, introduced special editions, and expanded news coverage. 1After Koshland's death in July 2007, Science Magazine published an article titled “In Memoriam: Dan Koshland, 1920–2007” (Vol. 317, p. 441) along with a page of personal staff remembrances. The article and remembrances can be found at: http://www.sciencemag.org/cgi/content/full/317/5837/441b 1After Koshland's death in July 2007, Science Magazine published an article titled “In Memoriam: Dan Koshland, 1920–2007” (Vol. 317, p. 441) along with a page of personal staff remembrances. The article and remembrances can be found at: http://www.sciencemag.org/cgi/content/full/317/5837/441b Among Koshland's many honors were the Welch Award in Chemistry (2006), the Albert Lasker Award for Special Achievement in Medical Science (1998), the National Medal of Science (1990), the ASBMB Merck Award (1990), the Rosenstiel Award (1984), the American Chemical Society's Pauling and Edgar Fahs Smith awards (1979), and election to the National Academy of Sciences and the American Academy of Arts and Sciences. Koshland was president of the American Society of Biological Chemists in 1973 and a member of the Journal of Biological Chemistry Editorial Board from 1961 to 1972. Koshland's wife of 52 years, Marian, was an eminent immunologist at Brookhaven and Berkeley who worked on a cholera vaccine and the behavior of antibodies. She died of lung cancer in 1997. To honor the memory of his wife, Koshland endowed the National Academy of Sciences with a $25 million gift to establish the Marian Koshland Science Museum. The museum focuses on increasing the public understanding of science, which was one of Marian's passions. 2Biographical information on Daniel E. Koshland was taken from Ref. 1Koshland Jr., D.E. How to get paid for having fun..Annu. Rev. Biochem. 1996; 65: 1-13Crossref PubMed Scopus (4) Google Scholar. 2Biographical information on Daniel E. Koshland was taken from Ref. 1Koshland Jr., D.E. How to get paid for having fun..Annu. Rev. Biochem. 1996; 65: 1-13Crossref PubMed Scopus (4) Google Scholar.
Source: Journal of Biological Chemistry
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1544227855