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The Role of Binding Energy in Catalysis: the Work of William P. Jencks

Open AccessPublished:November 05, 2010DOI:https://doi.org/10.1074/jbc.O110.000239
      William Platt Jencks (1927–2007) was born in Bar Harbor, Maine. He became interested in chemistry when he received a chemistry set for Christmas in 1934. He immediately carried out one of the experiments described in the instructions, the addition of dilute acid to a sulfide salt to produce H2S. The experiment was so successful that his house had to be evacuated due to the smell of rotten eggs. According to Jencks, “My family and I did not find it necessary to replicate this experiment” (
      • Jencks W.P.
      From chemistry to biochemistry to catalysis to movement.
      ).
      Jencks enrolled at Harvard College, intending to study chemistry. However, after taking a first year course in chemistry that “described a large number of chemical reactions, one after the other, with no indication of what was interesting about any of them” (
      • Jencks W.P.
      From chemistry to biochemistry to catalysis to movement.
      ), he switched his major to English. Despite this change in the direction of his studies, Jencks ended up entering Harvard Medical School after his junior year because he wasn't sure what else to do.
      After completing his first year of medical school, Jencks spent a summer at the Marine Biological Laboratory in Woods Hole, taking courses and doing research on lobster shell pigments with Journal of Biological Chemistry (JBC) Classic author George Wald (
      • Brown P.K.
      • Wald G.
      JBC Classics
      ). He received his M.D. in 1951 and then interned at Peter Bent Brigham Hospital in Boston. However, after a while, Jencks found medicine to be “a very broad field in which it would be difficult to obtain definitive answers to fundamental problems” (
      • Jencks W.P.
      From chemistry to biochemistry to catalysis to movement.
      ). Wald suggested Jencks try doing research at Massachusetts General Hospital with Nobel laureate Fritz Lipmann (who was featured in a previous JBC Classic (
      • Lipmann F.
      JBC Classics
      )). Jencks ended up spending 2 years with Lipmann, studying coenzyme A transferase, which led to his longtime interest in the physical organic chemistry of acyl transfer reactions. After leaving Massachusetts General Hospital, Jencks spent a year doing postdoctoral studies at Harvard University with Nobel laureate Robert Woodward before joining the faculty at Brandeis University in 1957, serving as assistant, associate, and then full professor of biochemistry. He retired in 1996 as professor emeritus of biochemistry.
      During his 39 years at Brandeis University, Jencks studied the mechanisms by which enzymes facilitate chemical reactions of molecules that are not otherwise inclined to react at a useful rate.
      The JBC Classic reprinted here looks at the noncovalent interactions between succinyl-CoA 3-ketoacid coenzyme A transferase and coenzyme A. In the paper, Jencks and Carol A. Fierke used a small coenzyme A analog, methylmercaptopropionate, to show that noncovalent interactions between the enzyme and the side chain of CoA are responsible for the reaction rate increase brought about by the enzyme. They report that interaction between the enzyme and the pantetheine moiety of CoA provides the majority of substrate destabilization and rate acceleration, whereas the interaction with the 3′-phospho-ADP1 moiety provides binding energy that overcomes this destabilization and permits significant binding of acyl-CoA substrates to the enzyme. This paper helped to illuminate a striking example of the role of binding energy in catalysis.
      Jencks received many honors and awards for his contributions to science, including memberships in the National Academy of Sciences (1971) and the American Philosophical Society (1995) and foreign membership in the Royal Society. He also received the 1962 American Chemical Society (ACS) Award in Biological Chemistry, the 1993 American Society of Biological Chemists Award, the 1995 ACS James Flack Norris Award in Physical Organic Chemistry, and the 1996 ACS Repligen Award for Chemistry of Biological Processes.
      Biographical information on William P. Jencks was taken from Refs.
      • Jencks W.P.
      From chemistry to biochemistry to catalysis to movement.
      and
      • Richard J.P.
      • Kirsch J.F.
      William Platt Jencks.
      .
      1Biographical information on William P. Jencks was taken from Refs.
      • Jencks W.P.
      From chemistry to biochemistry to catalysis to movement.
      and
      • Richard J.P.
      • Kirsch J.F.
      William Platt Jencks.
      .

      REFERENCES

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        From chemistry to biochemistry to catalysis to movement.
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        • JBC Classics
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        • Lipmann F.
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        J. Biol. Chem. 1945; 160: 173-190
        • Richard J.P.
        • Kirsch J.F.
        William Platt Jencks.
        Proc. Am. Philos. Soc. 2009; 153: 97-101