On the mechanism of action of vitamin B12: Theoretical studies of the 2-methyleneglutarate mutase catalyzed rearrangement

Journal of the American Chemical Society

Volumn 121, Issue 5, 1999, Pages 1037-1044

  Smith, David M ^a   Golding, Bernard T ^b   Radom, Leo ^a  

^a AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CYANOCOBALAMIN; GLUTARIC ACID DERIVATIVE; MUTASE;

ARTICLE; CATALYSIS; CONFORMATIONAL TRANSITION; DRUG PROTEIN BINDING; ENZYME ACTIVITY; STRUCTURE ANALYSIS;

EID: 0033540690     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9827245     Document Type: Article

References (65)

1. 12-Proteins; Kräutler, B., Arigoni, D., Golding, B. T., Eds.; Wiley-VCH: Weinheim, 1998.
2. Barker, H. A.; Smyth, R. D.; Wilson, R. M.; Weissbach, H. J. Biol. Chem. 1959, 234, 320-328.
3. Golding, B. T.; Buckel, W. Corrin-dependent Reactions. In Comprehensive Biological Catalysis; Sinnott, M. L., Ed.; Academic Press: London, 1997; Vol. III, pp 239-259. The stereochemistry for the β-lysine 5,6-aminomutase catalyzed reaction has not yet been established.
4. (a) Dowd, P.; Shapiro, M.; Kang, D. J. Am. Chem. Soc. 1975, 97, 4754.
5. (b) Fountoulakis, M.; Retey, J. Chem. Ber. 1980, 113, 650-668.
6. 12; Dolphin, D., Ed.; Wiley: New York, 1982; Vol. 1; pp 543-582.
7. (d) Wollowitz, S.; Halpern, J. J. Am. Chem. Soc. 1988, 110, 3112-3120.
8. (e) Ashwell, S.; Davies, A. G.; Golding, B. T.; Hay-Motherwell, R.; Mwesigye-Kibende, S. J. Chem. Soc., Chem. Commun. 1989, 1483-1485.
9. (f) Anderson, R. J.; Ashwell, S.; Dixon, R. M.; Golding, B. T. J. Chem. Soc., Chem. Commun. 1990, 70-72.
10. (g) Finke, R. G. In Molecular Mechanisms in Bioorganic Processes; Bleasdale C., Golding B. T., Eds.; The Royal Society of Chemistry: Cambridge, 1990; pp 244-280.
11. (h) Darbre, T.; Keese, R.; Siljegovic, V.; Wollebgygi, A. Helv. Chim. Acta 1996, 79, 2100.
12. (i) Hisaeda, Y.; Ogawa, A.; Ohno, T.; Murakami, Y. Inorg. Chim. Acta 1998, 273, 299-309.
13. (a) Golding, B. T.; Radom, L. J. Chem. Soc., Chem. Commun. 1973, 939-941.
14. (b) Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1976, 98, 6331-6338.
15. (a) Eggerer, H.; Stadtman, E. R.; Overath, P.; Lynen, F. Biochem. Z. 1960, 333, 1-9.
16. (b) Halpern, J. Ann. N. Y. Acad. Sci. 1974, 239, 2-21.
17. (a) Finke, R. G.; Schiraldi, D. A.; Mayer, B. J. Coord. Chem. Rev. 1984, 54, 1-22.
18. (b) Halpern, J. Science 1985, 227, 869-875.
19. Zelder, O.; Beatrix, B.; Leutbecher, U.; Buckel, W. Eur. J. Biochem. 1994, 226, 577-585.
20. (a) Luschinsky-Drennan, C.; Huang, S.; Drummond, J. T.; Matthews, R. G.; Ludwig, M. L. Science 1994, 266, 1669-1674.
21. (b) Mancia, F.; Keep, N. H.; Nakagawa, A.; Leadlay, P. F.; McSweeney, S.; Rasmussen, B.; Bosecke, P.; Diat, O.; Evans, P. R. Structure 1996, 4, 339-350.
22. He, M.; Dowd, P. J. Am. Chem. Soc. 1998, 120, 1133-1137.
23. Bothe, H.; Darley, D. J.; Albracht, S. P. J.; Gerfen, G. J.; Golding, B. T.; Buckel, W. Biochemistry 1998, 37, 4105-4113.
24. Beatrix, B.; Zelder, O.; Kroll, F. K.; Orlygsson, G.; Golding, B. T.; Buckel, W. Angew. Chem., Int. Ed. Engl. 1995, 34, 2398-2401. During the inhibition of 2-methyleneglutarate mutase by acrylate, it was found that a plot of 1/v versus the square of the acrylate concentration gave a straight line (Dixon plot, ν = initial velocity). This linear correlation suggests that two acrylate molecules are involved in the inhibition of the enzyme.
25. (a) Kung, H. F.; Cederbaum, S.; Tsai, L.; Stadtman, T. C. Proc. Natl. Acad. Sci. U.S.A. 1970, 65, 978.
26. (b) Buckel, W.; Golding, B. T. Chem. Soc. Rev. 1996, 26, 329-337.
27. (a) Kung, H. F.; Tsai, L. J. Biol. Chem. 1971, 246, 6436-6443.
28. (b) Hartrampf, G.; Buckel, W. Eur. J. Biochem. 1986, 156, 301-304.
29. Dowd, P.; Hershline, R. J. Chem. Soc., Perkin. Trans. 2 1988, 61-70.
30. Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley: New York, 1986.
31. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G. A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.; Head-Gordon, M.; Gonzalez, C.; Pople, J. A. GAUSSIAN 94 (Rev. E.2) (Gaussian, Inc., Pittsburgh, 1995).
32. Mayer, P. M.; Parkinson, C. J.; Smith, D. M.; Radom, L. J. Chem. Phys. 1998, 108, 604-615.
33. See, for example: (a) Newcombe, M.; Glenn, A. G. J. Am. Chem. Soc. 1989, 111, 275-277. (b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 347- 359. (c) Beckwith, A. L. J.; Bowry, V. J. Am. Chem. Soc. 1994, 116, 2710- 2716. (d) Martinez, F. N.; Schlegel, H. B.; Newcombe, M. J. Org. Chem. 1996, 61, 8547-8550. (e) Smith, D. M.; Nicolaides, A.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1998, 120, 10223-10233.
34. See, for example: (a) Newcombe, M.; Glenn, A. G. J. Am. Chem. Soc. 1989, 111, 275-277. (b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 347-359. (c) Beckwith, A. L. J.; Bowry, V. J. Am. Chem. Soc. 1994, 116, 2710- 2716. (d) Martinez, F. N.; Schlegel, H. B.; Newcombe, M. J. Org. Chem. 1996, 61, 8547-8550. (e) Smith, D. M.; Nicolaides, A.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1998, 120, 10223-10233.
35. See, for example: (a) Newcombe, M.; Glenn, A. G. J. Am. Chem. Soc. 1989, 111, 275-277. (b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 347- 359. (c) Beckwith, A. L. J.; Bowry, V. J. Am. Chem. Soc. 1994, 116, 2710-2716. (d) Martinez, F. N.; Schlegel, H. B.; Newcombe, M. J. Org. Chem. 1996, 61, 8547-8550. (e) Smith, D. M.; Nicolaides, A.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1998, 120, 10223-10233.
36. See, for example: (a) Newcombe, M.; Glenn, A. G. J. Am. Chem. Soc. 1989, 111, 275-277. (b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 347- 359. (c) Beckwith, A. L. J.; Bowry, V. J. Am. Chem. Soc. 1994, 116, 2710- 2716. (d) Martinez, F. N.; Schlegel, H. B.; Newcombe, M. J. Org. Chem. 1996, 61, 8547-8550. (e) Smith, D. M.; Nicolaides, A.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1998, 120, 10223-10233.
37. See, for example: (a) Newcombe, M.; Glenn, A. G. J. Am. Chem. Soc. 1989, 111, 275-277. (b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 347- 359. (c) Beckwith, A. L. J.; Bowry, V. J. Am. Chem. Soc. 1994, 116, 2710- 2716. (d) Martinez, F. N.; Schlegel, H. B.; Newcombe, M. J. Org. Chem. 1996, 61, 8547-8550. (e) Smith, D. M.; Nicolaides, A.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1998, 120, 10223-10233.
38. See, for example: (a) Wong, M. W.; Radom, L. J. Phys. Chem. 1995, 99, 8582-8588. (b) Wong, M. W.; Radom, L. J. Phys. Chem. 1998, 102, 2237-2245.
39. See, for example: (a) Wong, M. W.; Radom, L. J. Phys. Chem. 1995, 99, 8582-8588. (b) Wong, M. W.; Radom, L. J. Phys. Chem. 1998, 102, 2237-2245.
40. See, for example: (a) Russell, J. J.; Rzepa, H. S.; Widdowson, D. A. J. Chem. Soc., Chem. Commun. 1983, 625-627. (b) Greenberg, A.; Liebman, J. F. In Energetics of Organic Free Radicals, 1st ed.; Simoes, J. A. M., Greenberg, A., Liebman, J. F., Eds.; Blackie Academic and Professional: London, 1996; Vol. 4; pp 224-294.
41. See, for example: (a) Russell, J. J.; Rzepa, H. S.; Widdowson, D. A. J. Chem. Soc., Chem. Commun. 1983, 625-627. (b) Greenberg, A.; Liebman, J. F. In Energetics of Organic Free Radicals, 1st ed.; Simoes, J. A. M., Greenberg, A., Liebman, J. F., Eds.; Blackie Academic and Professional: London, 1996; Vol. 4; pp 224-294.
42. Hoz, T.; Sprecher, M.; Basch, H. J. Phys. Chem. 1985, 89, 1664-1670.
43. Lindsay, D. A.; Lusztyk, J.; Ingold, K. U. J. Am. Chem. Soc. 1984, 106, 7087-7093.
44. Smith, D. M.; Golding, B. T.; Radom, L., to be published.
45. Hoz, T.; Sprecher, M.; Basch, H. THEOCHEM 1987, 150, 51-65.
46. For further applications of protonation, see: George, P.; Glusker, J. P.; Bock, C. W. J. Am. Chem. Soc. 1997, 119, 7065-7074.
47. See, for example: Mayer, P. M.; Glukhovtsev, M. N.; Gauld, J. W.; Radom, L. J. Am. Chem. Soc. 1997, 119, 12889.
48. Roscoe, J. M.; Jayaweera, I. S.; Mackenzie, A. L.; Pacey, P. D. Int. J. Chem. Kinet. 1996, 28, 181-193.
49. (a) Sieck, L. W.; Gordon, R.; Ausloos, P. J. Am. Chem. Soc. 1972, 94, 7157-7159.
50. (b) Qin, X. Z.; Williams, F. Tetrahedron 1986, 42, 6301-6314.
51. (c) Lunell, S.; Yin, I.; Huang, M. B. Chem. Phys. 1989, 139, 293-299.
52. (a) Du, P.; Hrovat, D. A.; Borden, W. T. J. Am. Chem. Soc. 1988, 110, 3405-3412.
53. (b) Krogh-Jespersen, K.; Roth, H. D. J. Am. Chem. Soc. 1992, 114, 8388-8394.
54. (c) Skancke, A. J. Phys. Chem. 1995, 99, 13886-13889.
55. Lee, A. Y.; Stewart, J. D.; Clardy, J.; Ganem, B. Chem. Biol. 1995, 2, 195-203.
56. In this paper, all relative energies involving 9 correspond to the separated species. We note that in the course of our investigations we found hydrogen-bonded complexes between the 2-acrylic acid radical and acrylic acid that were more stable than the separated species but these are not discussed further in the present work.
57. The stereochemistry indicated for 10 corresponds to the lowest energy B3-LYP/6-31G(d) conformation (see Figure 3). This stereochemistry has not yet been established experimentally. However, if a cycylopropyl-carbinyl radical such as 10 is an intermediate, it must have R stereochemistry at the carbon atom corresponding to the chiral center in (R)-3-methylitaconate.
58. Edwards, C. H.; Golding, B. T.; Kroll, F.; Beatrix, B.; Broker, G.; Buckel, W. J. Am. Chem. Soc. 1996, 118, 4192-4193.
59. -1 in favor of the bent-coplanar structure for the 2-acrylic acid radical.
60. -1.
61. For a discussion of the partial-proton-transfer concept in the context of enzyme-catalyzed reactions, see: Smith, D. M.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1999, 121, in press.
62. -1 (6-311+G(3df,2p)). Both values were obtained with the inclusion of MP2(full)/6-31G(d) zero-point vibrational energies.
63. 396 suggest that H-atom abstraction is substantially rate-limiting in the overall transformation. Our calculations are consistent with the same conclusions for 2-methyleneglutarate mutase if the addition/elimination mechanism is in operation. However, in the case of the fragmentation/recombination mechanism, its higher barrier should cause it to become the rate-limiting step.
64. (b) Marsh, E. N. G. Biochemistry 1995, 34, 7542-7547.
65. The 2-acrylic-acid-radical (a component of 9) is shown in its lowest energy B3-LYP/6-31G(d) conformation. The conformational details of this species differ among the various theoretical procedures used. For a discussion, see text and note 35.