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Publicly Available Published by De Gruyter July 8, 2011

Enzymatic catalysis of proton transfer and decarboxylation reactions

John P. Richard

Deprotonation of carbon and decarboxylation at enzyme active sites proceed through the same carbanion intermediates as for the uncatalyzed reactions in water. The mechanism for the enzymatic reactions can be studied at the same level of detail as for nonenzymatic reactions, using the mechanistic tools developed by physical organic chemists. Triosephosphate isomerase (TIM)-catalyzed interconversion of D-glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) is being studied as a prototype for enzyme-catalyzed proton transfer, and orotidine monophosphate decarboxylase (OMPDC)-catalyzed decarboxylation of orotidine 5'-monophosphate (OMP) is being studied as a prototype for enzyme-catalyzed decarboxylation. 1H NMR spectroscopy is an excellent analytical method to monitor proton transfer to and from carbon catalyzed by these enzymes in D2O. Studies of these partial enzyme-catalyzed exchange reactions provide novel insight into the stability of carbanion reaction intermediates, which is not accessible in studies of the full enzymatic reaction. The importance of flexible enzyme loops and the contribution of interactions between these loops and the substrate phosphodianion to the enzymatic rate acceleration are discussed. The similarity in the interactions of OMPDC and TIM with the phosphodianion of bound substrate is emphasized.


Conference

International Conference on Physical Organic Chemistry (ICPOC-20), International Conference on Physical Organic Chemistry, ICPOC, Physical Organic Chemistry, 20th, Busan, Korea, 2010-08-22–2010-08-27


References

1 10.1038/161707a0, L. Pauling. Nature161, 707 (1948).Search in Google Scholar

2 10.1021/ja00052a028, T. L. Amyes, J. P. Richard. J. Am. Chem. Soc.114, 10297 (1992).Search in Google Scholar

3 10.1021/ja953664v, T. L. Amyes, J. P. Richard. J. Am. Chem. Soc.118, 3129 (1996).Search in Google Scholar

4 10.1021/ja982692l, J. P. Richard, G. Williams, J. Gao. J. Am. Chem. Soc.121, 715 (1999).Search in Google Scholar

5 10.1021/ja0125321, J. P. Richard, G. Williams, A. C. O’Donoghue, T. L. Amyes. J. Am. Chem. Soc.124, 2957 (2002).Search in Google Scholar

6 10.1021/ja001749c, A. Rios, T. L. Amyes, J. P. Richard. J. Am. Chem. Soc.122, 9373 (2000).Search in Google Scholar

7 10.1021/ja9714346, A. Rios, J. P. Richard. J. Am. Chem. Soc.119, 8375 (1997).Search in Google Scholar

8 10.1021/ja026267a, A. Rios, J. P. Richard, T. L. Amyes. J. Am. Chem. Soc.124, 8251 (2002).Search in Google Scholar

9 10.1016/S1367-5931(01)00258-7, J. P. Richard, T. L. Amyes. Curr. Op. Chem. Biol.5, 626 (2001).Search in Google Scholar

10 10.1016/j.bioorg.2004.05.002, J. P. Richard, T. L. Amyes. Bioorg. Chem.32, 354 (2004).Search in Google Scholar PubMed

11 T. L. Amyes, J. P. Richard. In Hydrogen-Transfer Reactions, Vol. 3, Biological Aspects I-II, J. T. Hynes, J. P. Klinman, H.-H. Limbach, R. L. Schowen (Eds.), pp. 949–973, Wiley-VCH, Weinheim (2007).Search in Google Scholar

12 10.1242/jeb.00516, K. A. Webster. J. Exp. Biol.206, 2911 (2003).Search in Google Scholar

13 10.1098/rstb.1991.0039, J. R. Knowles. Philos. Trans. R. Soc. London, Ser. B332, 115 (1991).Search in Google Scholar

14 I. A. Rose. Brookhaven Symp. Biol.15, 293 (1962).10.1063/1.3058226Search in Google Scholar

15 10.1016/S0022-2836(02)00649-6, N. Nagano, C. A. Orengo, J. M. Thornton. J. Mol. Biol.321, 741 (2002).Search in Google Scholar

16 10.1021/cr030191z, R. Sterner, B. Hocker. Chem. Rev.105, 4038 (2005).Search in Google Scholar PubMed

17 10.1126/science.7809611, A. Radzicka, R. Wolfenden. Science267, 90 (1995).Search in Google Scholar PubMed

18 10.1021/ar0000556, J. P. Richard, T. L. Amyes, M. M. Toteva. Acc. Chem. Res.34, 981 (2001).Search in Google Scholar PubMed

19 10.1021/bi047954c, A. C. O’Donoghue, T. L. Amyes, J. P. Richard. Biochemistry44, 2610 (2005).Search in Google Scholar PubMed

20 10.1021/bi047953k, A. C. O’Donoghue, T. L. Amyes, J. P. Richard. Biochemistry44, 2622 (2005).Search in Google Scholar PubMed

21 10.1021/ar50112a001, J. R. Knowles, W. J. Albery. Acc. Chem. Res.10, 105 (1977).Search in Google Scholar

22 10.1039/b714304d, A. C. O’Donoghue, T. L. Amyes, J. P. Richard. Org. Biomol. Chem.6, 391 (2008).Search in Google Scholar PubMed

23 10.1021/bi00670a026, J. M. Herlihy, S. G. Maister, W. J. Albery, J. R. Knowles. Biochemistry15, 5601 (1976).Search in Google Scholar PubMed

24 W. P. Jencks. Adv. Enzymol. Relat. Areas Mol. Biol.43, 219 (1975).Search in Google Scholar

25 10.1021/ja102408k, K. Toth, T. L. Amyes, B. M. Wood, K. Chan, J. A. Gerlt, J. P. Richard. J. Am. Chem. Soc.132, 7018 (2010).Search in Google Scholar PubMed PubMed Central

26 10.1021/ja076222f, K. Toth, T. L. Amyes, B. M. Wood, K. Chan, J. A. Gerlt, J. P. Richard. J. Am. Chem. Soc.129, 12946 (2007).Search in Google Scholar PubMed PubMed Central

27 10.1021/ja905081x, K.-Y. Wong, J. P. Richard, J. Gao. J. Am. Chem. Soc.131, 13963 (2009).Search in Google Scholar PubMed PubMed Central

28 10.1021/ja073679g, W.-Y. Tsang, J. P. Richard. J. Am. Chem. Soc.129, 10330 (2007).Search in Google Scholar PubMed PubMed Central

29 10.1021/ja905080e, W.-Y. Tsang, J. P. Richard. J. Am. Chem. Soc.131, 13952 (2009).Search in Google Scholar PubMed PubMed Central

30 10.1021/ja00284a018, R. M. Jarret, M. Saunders. J. Am. Chem. Soc.108, 7549 (1986).Search in Google Scholar PubMed

31 10.1021/ja710384t, T. L. Amyes, B. M. Wood, K. Chan, J. A. Gerlt, J. P. Richard. J. Am. Chem. Soc.130, 1574 (2008).Search in Google Scholar PubMed PubMed Central

32 10.1021/ja021073g, A. Sievers, R. Wolfenden. J. Am. Chem. Soc.124, 13986 (2002).Search in Google Scholar PubMed

33 10.1016/j.bioorg.2007.02.001, F. Y. Yeoh, R. R. Cuasito, C. C. Capule, F. M. Wong, W. Wu. Bioorg. Chem.35, 338 (2007).Search in Google Scholar PubMed PubMed Central

34 10.1073/pnas.030409797, B. G. Miller, A. M. Hassell, R. Wolfenden, M. V. Milburn, S. A. Short. Proc. Natl. Acad. Sci. USA97, 2011 (2000).Search in Google Scholar PubMed PubMed Central

35 10.1021/bi900623r, K. K. Chan, B. M. Wood, A. A. Fedorov, E. V. Fedorov, H. J. Imker, T. L. Amyes, J. P. Richard, S. C. Almo, J. A. Gerlt. Biochemistry48, 5518 (2009).Search in Google Scholar PubMed PubMed Central

36 10.1021/ja016754a, T. L. Amyes, A. C. O’Donoghue, J. P. Richard. J. Am. Chem. Soc.123, 11325 (2001).Search in Google Scholar PubMed

37 10.1021/bi700409b, T. L. Amyes, J. P. Richard. Biochemistry46, 5841 (2007).Search in Google Scholar PubMed PubMed Central

38 10.1021/ja00329a050, J. P. Richard. J. Am. Chem. Soc.106, 4926 (1984).Search in Google Scholar

39 10.1021/ja055493s, T. L. Amyes, J. P. Richard, J. J. Tait. J. Am. Chem. Soc.127, 15708 (2005).Search in Google Scholar PubMed

40 10.1021/bi8001743, W.-Y. Tsang, T. L. Amyes, J. P. Richard. Biochemistry47, 4575 (2008).Search in Google Scholar PubMed PubMed Central

41 10.1021/ar7002013, J. R. Morrow, T. L. Amyes, J. P. Richard. Acc. Chem. Res.41, 539 (2008).Search in Google Scholar PubMed PubMed Central

42 10.1021/bi101118g, M. K. Go, M. M. Malabanan, T. L. Amyes, J. P. Richard. Biochemistry49, 7704 (2010).Search in Google Scholar PubMed PubMed Central

43 10.1073/pnas.78.7.4046, W. P. Jencks. Proc. Natl. Acad. Sci. USA78, 4046 (1981).Search in Google Scholar PubMed PubMed Central

44 10.1021/bi900636c, M. K. Go, T. L. Amyes, J. P. Richard. Biochemistry48, 5769 (2009).Search in Google Scholar PubMed PubMed Central

45 10.1021/bi901064k, K. Toth, T. L. Amyes, B. M. Wood, K. K. Chan, J. A. Gerlt, J. P. Richard. Biochemistry48, 8006 (2009).Search in Google Scholar PubMed PubMed Central

46 10.1021/ja106104h, M. K. Go, T. L. Amyes, J. P. Richard. J. Am. Chem. Soc.132, 13525 (2010).Search in Google Scholar PubMed PubMed Central

47 10.1021/bi100538b, M. K. Go, A. Koudelka, T. L. Amyes, J. P. Richard. Biochemistry49, 5377 (2010).Search in Google Scholar PubMed PubMed Central

48 10.1021/bi00176a010, D. Joseph-McCarthy, E. Lolis, E. A. Komives, G. A. Petsko. Biochemistry33, 2815 (1994).Search in Google Scholar PubMed

49 10.1021/bi902174q, S. A. Barnett, T. L. Amyes, B. McKay Wood, J. A. Gerlt, J. P. Richard. Biochemistry49, 824 (2010).Search in Google Scholar PubMed PubMed Central

Online erschienen: 2011-7-8
Erschienen im Druck: 2011-7-8

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