Orbital steering in the catalytic power of enzymes: Small structural changes with large catalytic consequences

Science

Volumn 277, Issue 5323, 1997, Pages 202-206

  Mesecar, Andrew D ^a,b   Stoddard, Barry L ^c   Koshland Jr , Daniel E ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^c Fred Hutchinson Cancer Research Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CATALYSIS; CONFORMATIONAL TRANSITION; ENZYME CONFORMATION; ENZYME SUBSTRATE COMPLEX; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; PRIORITY JOURNAL;

CADMIUM; CALCIUM; CATALYSIS; CHEMISTRY, PHYSICAL; CRYSTALLOGRAPHY, X-RAY; HYDROGEN BONDING; ISOCITRATE DEHYDROGENASE; KINETICS; LIGANDS; MAGNESIUM; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; NAD; NADP; PROTEIN CONFORMATION;

EID: 0030879888     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.277.5323.202     Document Type: Article

References (63)

1. T. C. Bruice and V. K. Pandit, J. Am. Chem. Soc. 82, 5858 (1960); T. C. Bruice, Annu. Rev. Biochem. 45, 331 (1976).
2. T. C. Bruice and V. K. Pandit, J. Am. Chem. Soc. 82, 5858 (1960); T. C. Bruice, Annu. Rev. Biochem. 45, 331 (1976).
3. D. E. Koshland Jr., J. Theoret. Biol. 2, 75 (1962); _ and K. E. Neet, Annu. Rev. Biochem. 37, 359 (1968); D. A. Storm and D. E. Koshland Jr., Proc. Natl. Acad. Sci. U.S.A. 66, 445 (1970); A. Dafforn and D. E. Koshland, Jr., ibid. 68, 2463 (1971).
4. D. E. Koshland Jr., J. Theoret. Biol. 2, 75 (1962); _ and K. E. Neet, Annu. Rev. Biochem. 37, 359 (1968); D. A. Storm and D. E. Koshland Jr., Proc. Natl. Acad. Sci. U.S.A. 66, 445 (1970); A. Dafforn and D. E. Koshland, Jr., ibid. 68, 2463 (1971).
5. D. E. Koshland Jr., J. Theoret. Biol. 2, 75 (1962); _ and K. E. Neet, Annu. Rev. Biochem. 37, 359 (1968); D. A. Storm and D. E. Koshland Jr., Proc. Natl. Acad. Sci. U.S.A. 66, 445 (1970); A. Dafforn and D. E. Koshland, Jr., ibid. 68, 2463 (1971).
6. D. E. Koshland Jr., J. Theoret. Biol. 2, 75 (1962); _ and K. E. Neet, Annu. Rev. Biochem. 37, 359 (1968); D. A. Storm and D. E. Koshland Jr., Proc. Natl. Acad. Sci. U.S.A. 66, 445 (1970); A. Dafforn and D. E. Koshland, Jr., ibid. 68, 2463 (1971).
7. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
8. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
9. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
10. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
11. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
12. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
13. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
14. M. I. Page and W. P. Jencks, J. Am. Chem. Soc. 94, 8828 (1972); S. Schreiner, W. N. Lipscomb, D. A. Kleier, ibid. 98, 4770 (1976); F. M. Menger, Acc. Chem. Res. 18, 128 (1985); K. A. Brown and J. Kraut, Farraday Disc. 93, 217 (1992); W. M. Kati, S. A. Ackerson, R. Wolfenden, Biochemistry 31, 7356 (1992); D. D. Hackney, in The Enzymes, P. D. Boyer et al., Eds. (Academic Press, New York, ed. 3, 1990), pp. 1-36; D. W. Huhta et al., Acta Chem. Scand. (1992), p. 778; F. M. Menger, Acc. Chem. Res. 26, 206 (1993).
15. A. Warshel, Computer Modeling of Chemical Reaction in Enzymes and Solution (Wiley, New York, 1991).
16. L. Stryer, Biochemistry (Freeman, New York, ed. 3, 1988), p. 375.
17. J. H. Hurley et al., Proc. Natl. Acad. Sci. U.S.A. 86, 8635 (1989); J. H. Hurley, A. M. Dean, J. L. Sohl, D. E. Koshland Jr., R. M. Stroud, Science 249, 1012 (1990); B. L. Stoddard and D. E. Koshland Jr., Biochemistry 32, 9317 (1993).
18. J. H. Hurley et al., Proc. Natl. Acad. Sci. U.S.A. 86, 8635 (1989); J. H. Hurley, A. M. Dean, J. L. Sohl, D. E. Koshland Jr., R. M. Stroud, Science 249, 1012 (1990); B. L. Stoddard and D. E. Koshland Jr., Biochemistry 32, 9317 (1993).
19. J. H. Hurley et al., Proc. Natl. Acad. Sci. U.S.A. 86, 8635 (1989); J. H. Hurley, A. M. Dean, J. L. Sohl, D. E. Koshland Jr., R. M. Stroud, Science 249, 1012 (1990); B. L. Stoddard and D. E. Koshland Jr., Biochemistry 32, 9317 (1993).
20. D. B. Northrop and W. W. Cleland, J. Biol. Chem. 249, 2928 (1974); A. M. Dean and D. E. Koshland Jr., Biochemistry 32, 9302 (1993).
21. D. B. Northrop and W. W. Cleland, J. Biol. Chem. 249, 2928 (1974); A. M. Dean and D. E. Koshland Jr., Biochemistry 32, 9302 (1993).
22. J. M. Bolduc et al., Science 268, 1312 (1995); B. L. Stoddard, A. Dean, P. A. Bash, Nature Struct. Biol. 3, 590 (1996).
23. J. M. Bolduc et al., Science 268, 1312 (1995); B. L. Stoddard, A. Dean, P. A. Bash, Nature Struct. Biol. 3, 590 (1996).
24. D. W. Christianson and W. N. Lipscomb, Proc. Natl. Acad. Sci. U.S.A. 83, 7568 (1986); H. D. Bartunik, L. J. Bartunik, H. Viemann, Philos. Trans. R. Soc. London Ser. A 340, 209 (1992); X. Ding, B. F. Rasmussen, G. A. Petsko, D. Ringe, Biochemistry 33, 9285 (1994); I. Schlichting, J. Berendzin, G. N. Phillips, R. M. Sweet, Nature 371, 808 (1994).
25. D. W. Christianson and W. N. Lipscomb, Proc. Natl. Acad. Sci. U.S.A. 83, 7568 (1986); H. D. Bartunik, L. J. Bartunik, H. Viemann, Philos. Trans. R. Soc. London Ser. A 340, 209 (1992); X. Ding, B. F. Rasmussen, G. A. Petsko, D. Ringe, Biochemistry 33, 9285 (1994); I. Schlichting, J. Berendzin, G. N. Phillips, R. M. Sweet, Nature 371, 808 (1994).
26. D. W. Christianson and W. N. Lipscomb, Proc. Natl. Acad. Sci. U.S.A. 83, 7568 (1986); H. D. Bartunik, L. J. Bartunik, H. Viemann, Philos. Trans. R. Soc. London Ser. A 340, 209 (1992); X. Ding, B. F. Rasmussen, G. A. Petsko, D. Ringe, Biochemistry 33, 9285 (1994); I. Schlichting, J. Berendzin, G. N. Phillips, R. M. Sweet, Nature 371, 808 (1994).
27. D. W. Christianson and W. N. Lipscomb, Proc. Natl. Acad. Sci. U.S.A. 83, 7568 (1986); H. D. Bartunik, L. J. Bartunik, H. Viemann, Philos. Trans. R. Soc. London Ser. A 340, 209 (1992); X. Ding, B. F. Rasmussen, G. A. Petsko, D. Ringe, Biochemistry 33, 9285 (1994); I. Schlichting, J. Berendzin, G. N. Phillips, R. M. Sweet, Nature 371, 808 (1994).
28. J. H. Hurley, A. M. Dean, D. E. Koshland Jr., R. M. Stroud, Biochemistry 30, 8671 (1991).
29. J. P. Glusker, Adv. Prot. Chem. 42, 1 (1991); C. A. McPhalen, N. C. J. Strynadka, M. N. G. James, ibid., p. 77.
30. J. P. Glusker, Adv. Prot. Chem. 42, 1 (1991); C. A. McPhalen, N. C. J. Strynadka, M. N. G. James, ibid., p. 77.
31. J. Bajoratti, W. Hinrichs, W. Sänger, Nature 337, 481 (1989); P. Gros, A. V. Teplyakov, W. G. Hol, Proteins 12, 63 (1992).
32. J. Bajoratti, W. Hinrichs, W. Sänger, Nature 337, 481 (1989); P. Gros, A. V. Teplyakov, W. G. Hol, Proteins 12, 63 (1992).
33. M. F. Perutz, Mechanisms of Cooperativity and Allosteric Regulation in Proteins (Cambridge Univ. Press, New York, 1990).
34. R. F. Colman, J. Biol. Chem. 247, 215 (1972).
35. R. S. Ehrlich and R. F. Colman, Biochemistry 28, 2058 (1989); Biochim. Biophys. Acta 1246, 135 (1995).
36. R. S. Ehrlich and R. F. Colman, Biochemistry 28, 2058 (1989); Biochim. Biophys. Acta 1246, 135 (1995).
37. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
38. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
39. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
40. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
41. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
42. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
43. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
44. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
45. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
46. M. C. A Donkersloot and H. M. Buck, J. Am. Chem. Soc. 103, 6549, 6554 (1981); Y. D. Wu and K. N. Houk, ibid. 109, 2226 (1987); R. Sustman, W. Sicking, G. E. Schulz, Angew. Chem. Int. Ed. Engl. 28, 1023 (1989); M. J. Sherrod and F. M. Menger, J. Am. Chem. Soc. 111, 2611 (1989); I. H. Williams, A. B. Miller, G. M. Maggiora, ibid. 112, 530 (1990); P. L. Cummins and J. E. Gready, J. Comp. Chem. 11, 791 (1990); M. J. Sherrod and F. M. Menger, Tetrahedron Lett. 31, 459 (1990); N. Bodor, M. E. Brewster, J. J. Kaminski, J. Mol. Struct. Theorchem. 206, 315 (1990); Y. D. Wu, K. N. Houk, J. Am. Chem. Soc. 113, 2353 (1991); O. Almarsson and T. C. Bruice, ibid. 115, 2125 (1993).
47. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
48. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
49. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
50. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
51. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
52. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
53. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
54. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
55. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
56. P. A. Karplus and G. E. Schulz, J. Mol. Biol. 210, 163 (1989); C. Bystroff, S. J. Oatley, J. Kraut, Biochemistry 29, 3263 (1990); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, ibid. 31, 7264 (1992); M. D. Hall and L. J. Banaszak, J. Mol. Biol. 232, 213 (1993); M. A. McTigue, J. F. Davies II, B. T. Kaufman, J. Kraut, Biochemistry 32, 6855 (1993); D. H. Harrison, K. M. Bohren, D. Ringe, G. A. Petsko, K. H. Gabbay, ibid. 33, 2011 (1994); S. Ramaswamy, H. Eklund, B. V. Plapp, ibid., p. 5230; N. Tanaka et al., Structure 4, 33 (1996); J. B. Thoden, P. A. Frey, H. M. Holden, Protein Sci. 5, 2149 (1996); N. Tanaka et al., Biochemistry 35, 7715 (1996).
57. This strategy for data collection and for trapping reactive enzyme intermediate is advantageous because (i) the resolution is increased significantly (both data sets are measured to 1.9 Å resolution) and (ii), the structure of a complex that turns over very slowly at room temperature (such as NHDP in the active site of IDH) is physically trapped at the low temperature of data collection, allowing analysis of a transient population that displays dynamic movement and catalytic heterogeneity at higher temperatures.
58. Z. Otwinowski, Proceedings of the CCP4 Study Weekend: Data Collection and Processing, L. Sawyer, N. Isaacs, S. Bailey, Eds. (SERC Daresbury Laboratory, UK).
59. J. H. Hurley, R. Chen, A. M. Dean, Biochemistry 35, 5670 (1996).
60. J. Naveza, Acta Crystallogr. A 50, 157 (1994).
61. A. Brünger, X-PLOR, version 3.1 (Yale Univ. Press, New Haven, CT, 1992).
62. The structures of the bound complexes were compared by at least-squares superposition of alpha-carbons from the enzyme dimers by means of the protein design module of the program Quanta (Quanta96 X-ray Structure Analysis User's Reference, San Diego: Molecular Simulations, 1996).
63. 2+-NHDP complexes have been submitted to the Brookhaven Protein Data Base with accession numbers 1Al2 and 1Al3 respectively; the code number for the coordinates for the Y160F Laue complex in the PDB is 1IDE.