Understanding the mechanism of B12-dependent methylmalonyl-CoA mutase: Partial proton transfer in action

Journal of the American Chemical Society

Volumn 121, Issue 40, 1999, Pages 9388-9399

  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

COBAMAMIDE; METHYLMALONYL COENZYME A MUTASE;

ARTICLE; CATALYSIS; CHEMICAL REACTION; CRYSTAL STRUCTURE; ENZYME MECHANISM; PROTON TRANSPORT; STEREOCHEMISTRY; THEORY;

EID: 0033552235     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja991649a     Document Type: Article

References (95)

1. 12; Dolphin, D., Ed.; J Wiley & Sons: New York, 1982; Vol. 2, pp 357-379.
2. (a) 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.
3. (b) Mancia, F.; Evans, P. R. Structure 1998, 6, 711-720.
4. Thoma, N. H.; Meier, T. W.; Evans, P. R.; Leadlay, P. F. Biochemistry 1998, 37, 14386-14393.
5. Ludwig, M. L.; Matthews, R. G. Annu. Rev. Biochem. 1997, 66, 269-313.
6. (a) Eggerer, H.; Overath, P.; Lynen, F.; Stadtman, E. R. J. Am. Chem. Soc. 1960, 82, 2643-2644.
7. (b) Eggerer, H.; Stadtman, E. R.; Overath, P.; Lynen, F. Biochem. Z. 1960, 333, 1-9.
8. 12-Proteins; Krautler, B., Arigoni, D., Golding, B. T., Eds.; Wiley-VCH: Weinheim, 1998; pp 289-301.
9. 12-Proteins; Krautler, B., Arigoni, D., Golding, B. T., Eds.; Wiley-VCH: Weinheim, 1998; pp 289-301.
10. 12-Proteins; Krautler, B., Arigoni, D., Golding, B. T., Eds.; Wiley-VCH: Weinheim, 1998; pp 289-301.
11. 12-Proteins; Krautler, B., Arigoni, D., Golding, B. T., Eds.; Wiley-VCH: Weinheim, 1998; pp 289-301.
12. (a) Ingraham, L. L. Ann. N. Y. Acad. Sci. 1964, 112, 713-720.
13. (b) Merkelbach, I. I.; Becht, H. G. M.; Buck, H. M. J. Am. Chem. Soc. 1985, 107, 4037-4042.
14. (a) Pratt, J. M. Chem. Soc. Rev. 1985, 14, 161-170.
15. (b) Choi, G.; Choi, S.; Galan, A.; Wilk, B.; Dowd, P. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 3174-3176.
16. (a) He, M.; Dowd, P. J. Am. Chem. Soc. 1996, 118, 711.
17. (b) He, M.; Dowd, P. J. Am. Chem. Soc. 1998, 120, 1133-1137.
18. (a) Zhao, Y.; Such, P.; Rétey, J. Angew. Chem., Int. Ed. Engl. 1992, 31, 215-216.
19. (b) Zhao, Y.; Abend, A.; Kunz, M.; Such, P.; Rétey, J. Eur. J. Biochem. 1994, 225, 891-896.
20. (c) Padmakumar, R.; Banerjee, R. J. Biol. Chem. 1995, 270, 9295-9300.
21. (d) Padmakumar, R.; Padmakumar, R.; Banerjee, R. Biochemistry 1997, 36, 3713-3718.
22. (e) Abend, A.; Illich, V.; Rétey, J. Eur. J. Biochem. 1997, 249, 180-186.
23. Bothe, H.; Darley, D. J.; Albracht, S. P. J.; Gerfen, G. J.; Golding, B. T.; Buckel, W. Biochemistry 1998, 37, 4105-4113.
24. (a) Cockle, S. A.; Hill, H. A. O.; Williams, R. J. P.; Davies, S. P.; Foster, M. A. J. Am. Chem. Soc. 1972, 94, 275-276.
25. (b) Hartmanis, M. G. N.; Stadtman, T. C. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 76-79.
26. Orme-Johnson, W. H.; Beinert, H.; Blakley, R. L. J. Biol. Chem. 1974, 249, 2338-2343.
27. Babior, B. M.; Moss, T. H.; Orme-Johnson, W. H.; Beinert, H. J. Biol. Chem. 1974, 249, 4537-4544.
28. See, for example: (a) Rétey, J.; Robinson, J. A. In Stereospecificity in Organic Chemistry and Enzymology; Ebel, H. F., Ed.; Verlag Chemie: Weinheim, 1982; pp 185-207. (b) Beatrix, B.; Zelder, O.; Kroll, F. K.; Orlygsson, G.; Golding, B. T.; Buckel, W. Angew. Chem., Int. Ed. Engl. 1995, 34, 2398-2401.
29. See, for example: (a) Rétey, J.; Robinson, J. A. In Stereospecificity in Organic Chemistry and Enzymology; Ebel, H. F., Ed.; Verlag Chemie: Weinheim, 1982; pp 185-207. (b) Beatrix, B.; Zelder, O.; Kroll, F. K.; Orlygsson, G.; Golding, B. T.; Buckel, W. Angew. Chem., Int. Ed. Engl. 1995, 34, 2398-2401.
30. For a detailed discussion of the stereochemical aspects of the rearrangement, see section D.
31. Smith, D. M.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1999, 121, 1037-1044.
32. 2CHO) as the 3-propanal radical. This species may be better named as the 3-oxoprop-1-yl radical. Similarly, we have referred to 1 as the methylmalonyl-CoA-derived radical, 5 as the methylmalonyl-derived radical, 2 as the succinyl-CoA-related radical, and 6 as the succinyl-related radical.
33. Meier, T. W.; Thoma, N. H.; Leadlay, P. F. Biochemistry 1996, 35, 11791-11796.
34. George, P.; Glusker, J. P.; Bock, C. W. J. Am. Chem. Soc. 1997, 119, 7065-7074.
35. A preliminary account of this work has appeared: Smith, D. M.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1999, 121, 1383-1384.
36. Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley: New York, 1986.
37. 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, Revision E.2; Gaussian, Inc.: Pittsburgh, PA, 1995.
38. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C. Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.6; Gaussian, Inc.: Pittsburgh, PA, 1998.
39. MOLPRO 97 is a package of ab initio programs written by H.-J. Werner and P. J. Knowles, with contributions from J. Almlof, R. D. Amos, A. Berning, D. L. Cooper, M. J. O. Deegan, A. J. Dobbyn, F. Eckert, S. T. Elbert, C. Hampel, R. Lindh, W. A. Lloyd, W. Meyer, A. Nickless, K. Peterson, R. Pitzer, A. J. Stone, P. R. Taylor, M. E. Mura, P. Pulay, M. Schütz, H. Stoll, and T. Thorsteinsson.
40. Smith, D. M.; Nicolaides, A.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1998, 120, 10223-10233.
41. Mayer, P. M.; Parkinson, C. J.; Smith, D. M.; Radom, L. J. Chem. Phys. 1998, 108, 604-615.
42. -1.
43. Wong, M. W.; Radom, L. J. Phys. Chem. 1998, 102, 2237-2245.
44. (a) Parkinson, C. J.; Mayer, P. M.; Radom, L. Theor. Chim. Acta 1999, 102, 92-96.
45. (b) Parkinson, C. J.; Mayer, P. M.; Radom, L. Work in progress.
46. (c) Parkinson, C. J.; Radom, L. Work in progress.
47. Smith, D. M.; Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1999, 121, 5700-5704.
48. 1 structure is the one that most closely resembles the bound conformation of the substrate.
49. Giese, B.; Horler, H. Tetrahedron Lett. 1983, 24, 3221-3224.
50. The quoted barrier corresponds to the energy of the symmetrical structure, which, after inclusion of the zero-point energy, is higher than the two nonsymmetrical transition structures (see Supporting Information).
51. (a) Golding, B. T.; Radom, L. J. Chem. Soc., Chem. Commun. 1973, 939-941.
52. (b) Golding, B. T.; Radom, L. J. Am. Chem. Soc. 1976, 98, 6331-6338.
53. The additional proton can be either syn or anti to the carbon framework. The lowest-energy arrangement is the anti form (shown in Figure 2). The X-ray crystal structures (section E) suggest that, if a proton were to interact with the carbonyl oxygen, then it would do so from the face of the molecule consistent with this conformation. For reasons of consistency and biological relevance, we have maintained this arrangement for all subsequent examples involving protonation of the carbonyl group throughout this paper.
54. 38
55. Bouchoux, G.; Luna, A.; Tortajada, J. Int. J. Mass Spectrom. Ion Processes 1997, 167/168, 353-374.
56. Thibblin, A.; Jencks, W. P. J. Am. Chem. Soc. 1979, 101, 4963-4973.
57. Edward, J. T.; Wong, S. C.; Welch, G. Can. J. Chem. 1978, 59, 931-940.
58. +, and Cys and Tyr closer to HF.
59. + as the acid, the symmetrical species is a transition structure on the vibrationless surface.
60. (a) Gerlt, J. A.; Gassman, P. G. J. Am. Chem. Soc. 1993, 115, 11552-11568.
61. (b) Cleland, W. W.; Kreevoy, M. M. Science 1994, 264, 1887-1890.
62. (c) Frey, P. A.; Whitt, S. A.; Tobin, J. B. Science 1994, 264, 1927-1930.
63. (a) Scheiner, S.; Kar, T. J. Am. Chem. Soc. 1995, 117, 6970-6975.
64. (b) Shan, S.; Loh, S.; Herschlag, D. Science 1996, 272, 97-101.
65. (c) Garcia-Viloca, M.; Gonzalez-Lafont, A.; Lluch, J. M. J. Phys. Chem. A. 1997, 101, 3880-3886.
66. (a) Perrin, C. L.; Nielson, J. B. Annu. Rev. Phys. Chem. 1997, 48, 511-544.
67. (b) Tuckerman, M. E.; Marx, D.; Klein, M. L.; Parrinello, M. Science 1997, 275, 817-820.
68. (c) Ash, E. L.; Sudmeier, J. L.; DeFabo, E. C.; Bachovchin, W. W. Science 1997, 278, 1128-1132.
69. (d) Perrin, C. L.; Nielson, J. B.; Kim, Y. Ber. Bunsen-Ges. Phys. Chem. 1998, 102, 403-409.
70. Gilli, P.; Bertolasi, V.; Ferretti, V.; Gilli, G. J. Am. Chem. Soc. 1994, 116, 909-915.
71. (a) Guthrie, J. P. Chem. Biol. 1996, 3, 163-170.
72. (b) Pan, Y.; McAllister, M. J. Am. Chem. Soc. 1997, 119, 7561-7566.
73. (c) Pan, Y.; McAllister, M. J. Am. Chem. Soc. 1998, 120, 166-169.
74. (a) Warshel, A.; Papazyan, A.; Kollman, P. A. Science 1995, 269, 102-103.
75. (b) Warshel, A.; Papazyan, A. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 13665-13670.
76. The enolization step of citrate synthase could also be described in terms of partial proton transfer. See, for example: Mulholland, A. J.; Richards, W. G. J. Phys. Chem. B 1998, 102, 6635-6646.
77. 1 conformer for our calculations involving this molecule.
78. -1 in order to undergo the 1.2-shift. For further details regarding the various conformational aspects of this system, see Supporting Information.
79. -1.
80. 1 conformer shown in Figure 5 for the bulk of the calculations involving this molecule. See also Figure 7 and the Supporting Information.
81. Kellermeyer, R. W.; Alen, S. H. G.; Stjernholm, R.; Wood, H. G. J. Biol. Chem. 1964, 239, 2562-2569.
82. (a) Michenfelder, M.; Hull, W. E.; Rétey, J. Eur. J. Biochem. 1987, 168, 659-667.
83. (b) Hull, W. E.; Michenfelder, M.; Rétey, J. Eur. J. Biochem. 1988, 173, 191-201.
84. Buckel, W.; Golding, B. T. Chem. Soc. Rev. 1996, 26, 329-337.
85. See, for example: Bugg, T. An Introduction to Enzyme and Coenzyme Chemistry; Blackwell Scientific: Cambridge, MA, 1997; pp 210-211.
86. The rotation directions are defined as if one were looking at a Fischer projection of the molecule with the rotating group in front and the remainder of the structure behind. If both rotations are defined from the same Fischer projection, then they are actually in the same direction.
87. 2H rotation).
88. -1) transition structure in which these two functional groups are on opposite sides of the ring. The X-ray crystal structure suggests that the biologically relevant arrangement is TS:5→6, as shown in Schemes 3 and 5. This same energy ordering for the two transition structures was also found in ref 6d.
89. 36,51 The resulting structures have converged (or virtually converged) energy gradients and are thus considered sufficiently close to the stationary points for the zero-point energies to be reasonable.
90. 4+ rearrangement. For the zero-point contribution to the enthalpy, we used that obtained from the 5→6 rearrangement.
91. -1 lower in energy than the former. See Figure 9.
92. Rétey, J. Angew. Chem., Int. Ed. Engl. 1990, 29, 355-361.
93. The PDB code for the structure shown in Figure 10 is 5req. For information on the Protein Data Bank, see: (a) Abola, E. E.; Sussman, J. L.; Prilusky, J.; Manning, N. O. In Methods in Enzymology; Carter, C. W., Jr., Sweet, R. M., Eds.; Academic Press: San Diego, CA, 1997; Vol. 277, pp 556-571. (b) Sussman, J. L.; Lin, D.; Jiang, J.; Manning, N. O.; Prilusky, J.; Ritter, O.; Abola, E. E. Acta Crystallogr. 1998, D54, 1078-1084.
94. The PDB code for the structure shown in Figure 10 is 5req. For information on the Protein Data Bank, see: (a) Abola, E. E.; Sussman, J. L.; Prilusky, J.; Manning, N. O. In Methods in Enzymology; Carter, C. W., Jr., Sweet, R. M., Eds.; Academic Press: San Diego, CA, 1997; Vol. 277, pp 556-571. (b) Sussman, J. L.; Lin, D.; Jiang, J.; Manning, N. O.; Prilusky, J.; Ritter, O.; Abola, E. E. Acta Crystallogr. 1998, D54, 1078-1084.
95. 12-Proteins; Krautler, B., Arigoni, D., Golding, B. T., Eds.; Wiley-VCH: Weinheim, 1998; pp 217-226.