Acetyl-CoA enolization in citrate synthase: A quantum mechanical/molecular mechanical (QM/MM) study

Proteins: Structure, Function and Genetics

Volumn 27, Issue 1, 1997, Pages 9-25

  Mulholland, Adrian J ^a,b   Richards, W Graham ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b HARVARD UNIVERSITY   (United States)

Author keywords

CHARMM; enzyme reaction intermediate; Marcus formalism analysis; strong hydrogen bonds

Indexed keywords

ACETYL COENZYME A;

ARTICLE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME STABILITY; HYDROGEN BOND; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; PRIORITY JOURNAL;

ACETYL COENZYME A; BINDING SITES; CITRATE (SI)-SYNTHASE; HISTIDINE; HYDROGEN BONDING;

EID: 0031033361     PISSN: 08873585     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1097-0134(199701)27:1<9::AID-PROT3>3.0.CO;2-D     Document Type: Article

References (102)

1. Mulholland, A.J., Grant, G.H., Richards, W.G. Review: Computer modelling of enzyme catalysed reaction mechanisms. Prot. Eng. 6:133-147, 1993.
2. Field, M.J., Bash, P.A., Karplus, M. A Combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations. J. Comp. Chem. 11: 700-733, 1990.
3. Åqvist, J., Warshel, A. Simulation of enzyme reactions using valence bond force fields and other hybrid quantum/classical approaches. Chem. Rev. 93:2523-2544, 1993.
4. Walsh, C. "Enzymatic Reaction Mechanisms." New York: W.H. Freeman, 1979.
5. Thibblin, A., Jencks, W.P. Unstable carbanions: General acid catalysis of the cleavage of 1-phenylcyclopropanol and 1-phenyl-2-arylcyclopropanol anions. J. Am. Chem. Soc. 101:4963-4973, 1979.
6. Gerlt, J.A., Gassman, P.G. Understanding the rates of certain enzyme-catalyzed reactions: Proton abstraction from carbon acids, acyl-transfer reactions, and displacement reactions of phosphodiesters. Biochemistry 32: 11943-11952, 1993.
7. Cleland, W.W., Kreevoy, M.M. Low-barrier hydrogen bonds and enzymic catalysis. Science 264:1887-1890, 1994.
8. Usher, K.C., Remington, S.J., Martin, D.P., Drueckhammer, D.G. A very short hydrogen bond provides only moderate stabilization of an enzyme-inhibitor complex of citrate synthase. Biochemistry 33:7753-7759, 1994.
9. Rault-Leonardon, M., Atkinson, M.A.L., Slaughter, C.A., Moomaw, C.R., Srere, P.A. Azotobacter vinelandii citrate synthase. Biochemistry 34:257-263, 1995.
10. Remington, S.J. Structure and mechanism of citrate synthase. Curr. Top. Cell. Regul. 33:209-229, 1992.
11. Eggerer, H., Buckel, W., Lenz, H., Wunderwald, P., Gottschalk, G., Cornforth, J.W., Donninger, C., Mallaby, R., Redmond, J.W. Stereochemistry of enzymic citrate synthesis and cleavage. Nature 226:517-519, 1970.
12. Retey, J., Luthy, J., Arigoni, D. Fate of chiral acetates in the citric acid cycle. Nature 226:519-521, 1970.
13. Beeckmans, S. Some structural and regulatory aspects of citrate synthase. Int. J. Biochem. 16:341-351, 1984.
14. Kurz, L.C., Drysdale, G.R. Evidence from Fourier transform infrared spectroscopy for polarization of the carbonyl of oxaloacetate in the active site of citrate synthase. Biochemistry 26:2623-2627, 1987.
15. Pettersson, G., Lill, U., Eggerer, H. Mechanism of interaction of citrate synthase with citryl-CoA. Eur. J. Biochem. 182:119-124, 1989.
16. Eggerer, H. Zum Mechanismus der biologischen Umwandlung von Citronensaure. VI. Citrat-synthase ist eine Acetyl-CoA Enolase. Biochem. Z. 343:111-138, 1965.
17. Wlassics, I.D., Anderson, V.E. Citrate synthase stabilizes the enethiolate of acetyldithio coenzyme A. Biochemistry 28:1627-1633, 1989.
18. Clark, J.D., O'Keefe, S.J., Knowles, J.R. Malate synthase: Proof of a stepwise Claisen condensation using the double-isotope fractionation test. Biochemistry 27:5961-5971, 1988.
19. Karpusas, M., Branchaud, B., Remington, S.J. Proposed mechanism for the condensation reaction of citrate synthase: 1.9 Å structure of the ternary complex with oxaloacetate and carboxymethyl coenzyme A. Biochemistry 29:2213-2219, 1990.
20. Alter, G.M., Casazza, J.P., Zhi, W., Nemeth, P., Srere, P.A., Evans, C.T. Mutation of essential catalytic residues in pig citrate synthase. Biochemistry 29:7557-7563, 1990.
21. Bash, P.A., Field, M.J., Davenport, R.C., Petsko, G.A., Ringe, D., Karplus, M. Computer simulation and analysis of the reaction pathway of triosephosphate isomerase. Biochemistry 30:5826-5832, 1991.
22. a balance: The case of triose phosphate isomerase (TIM)? J. Am. Chem. Soc. 117:9855-9862, 1995.
23. Lodi, P., Knowles, J.R. Neutral imidazole is the electrophile in the reaction catalyzed by triosephosphate isomerase: Structural origins and catalytic implications. Biochemistry 30:6948-6956, 1991.
24. Remington, S.J. Mechanisms of citrate synthase and related enzymes (triosephosphate isomerase and mandelate racemase). Curr. Opin. Struct. Biol. 2:730-735, 1992.
25. Gerlt, J.A., Gassman, P.G. An explanation of rapid enzyme-catalyzed proton abstraction from carbon acids: Importance of late transition states in concerted mechanisms. J. Am. Chem. Soc. 115:11552-11568, 1993.
26. Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., Karplus, M. CHARMM: A program for macromolecular energy, minimization and dynamics calculations. J. Comp. Chem. 4:187-217, 1983.
27. Dewar, M.J.S., Zoebisch, E.G., Healy, E.F., Stewart, J.J.P. AM1: A new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 107:3902-3909, 1985.
28. Lyne, P., Mulholland, A.J., Richards, W.G. Insights into chorismate mutase catalysis from a combined QM/MM simulation of the enzyme reaction. J. Am. Chem. Soc. 117:11345-11350, 1995.
29. Barnes, J.A., Williams, I.H. Quantum mechanical/molecular mechanical approaches to transition state structure: Mechanism of sialidase action. Biochem. Soc. Trans. 24: 263-268, 1996.
30. Bash, P.A., Field, M.J., Karplus, M. Free energy perturbation method for chemical reactions in the condensed phase: A dynamical approach based on a combined quantum and molecular mechanical potential. J. Am. Chem. Soc. 109:8092-8094, 1987.
31. Sehgal, A., Shao, L., Gao, J. Transition structure and substituent effects on aqueous acceleration of the Claisen rearrangement. J. Am. Chem. Soc. 117:11337-11340, 1995.
32. Barnes, J.A., Williams, I.H. Theoretical modelling of kinetic isotope effects for glycoside hydrolysis in aqueous solution by a hybrid quantum-mechanical/molecular-mechanical method. J. Chem. Soc. Chem. Commun. 193-194, 1996.
33. Gao, J., Xia, X. A priori evaluation of aqueous polarization effects through Monte Carlo QM-MM simulations. Science 258:631-635, 1991.
34. Elcock, A.H., Lyne, P.D., Mulholland, A.J., Nandra, A., Richards, W.G. Combined Quantum and molecular mechanical study of DNA cross-linking by nitrous acid. J. Am. Chem. Soc. 117:4706-4707, 1995.
35. CHARMM Version 23: Contact Prof. M. Karplus, Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, MA 02138.
36. Stewart, J.J.P. MOPAC: A semi-empirical molecular orbital program. J. Comput Aided Mol. Design 4:1-105, 1990.
37. Frisch, M.J., Head-Gordon, M., Trucks, G.W., Foresman, J.B., Schlegel, H.B., Raghavachari, K., Robb, M., Binkley, J.S., Gonzalez, C., Defrees, D.J., Fox, D.J., Whiteside, R.A., Seeger, R., Melius, C.F., Baker, J., Martin, L.R., Kahn, L.R., Stewart, J.J.P., Topiol, S., Pople, J.A. Gaussian 90 Revision J. Gaussian Inc., Pittsburgh, PA, 1990.
38. Remington, S., Wiegand, G., Huber, R. Crystallographic refinement and atomic models of two different froms of citrate synthase at 2.7 and 1.7 Å resolution. J. Mol. Biol. 158:111-152, 1982.
39. Kollmann-Koch, A., Eggerer, H. Ligand-induced conformational changes of citrate synthase studied with the fluorescent probe 8-anilinonaphthalene 1-sulfonate. Eur. J. Biochem. 185:441-447, 1989.
40. Ech-Cherif El-Kettani, M.A., Zakrzewska, K., Durup, J., Lavery, R. An analysis of the conformational paths of citrate synthase. Proteins 16:393-407, 1993.
41. Lesk, A.M., Chothia, C. Mechanisms of domain closure in proteins. J. Mol. Biol. 174:175-191, 1984.
42. Löujhlein-Werhahn, G., Bayer, E., Bauer, B., Eggerer, H. Hysteretic behaviour of citrate synthase: Alternating sites during the catalytic cycle. Eur. J. Biochem. 133: 665-672, 1983.
43. Man, W.-J., Li, Y., O'Connor, D., Wilton, D.C. Conversion of citrate synthase into citryl-Coa lyase as a result of mutation of the active-site aspartic acid residue to glutamic acid. Biochem. J. 280:521-526, 1991.
44. Karpusas, M., Holland, D., Remington, S.J. 1.9-Å Structures of ternary complexes of citrate synthase with D-and L-malate: Mechanistic implications. Biochemistry 30: 6024-6031, 1991.
45. Bernstein, F.C., Koetzle, T.F., William, G.J.B., Meyer, E.J., Jr., Brice, M.D., Rogers, J.R., Kennerd, O., Shimanouchi, T. The protein data bank: A computer-based archival file for macromolecular structures. J. Mol. Biol. 112: 532-542, 1977.
46. Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., Klein, M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79: 926-935, 1983.
47. Levitt, M., Park, B.H. Water: Now you see it, now you don't. Structure 1:223-226, 1993.
48. Stewart, J.J.P. Optimization of parameters for semiempirical methods. I. Method. J. Comp. Chem. 10:209-220, 1989.
49. n, n=2-4. J. Chem. Soc. Perkin Trans. 2:943-951, 1990.
50. Brunger, A.T., Karplus, M. Polar hydrogen positions in proteins: Empirical energy placement and neutron diffraction comparison. Proteins 4:148-156, 1988.
51. Durup, J. Protein molecular dynamics constrained to slow modes: Theoretical approach based on a hierarchy of local modes with a set of holonomic constraints. J. Phys. Chem. 95:1817-1829, 1991.
52. QUANTA 3.3. Molecular Simulations, Inc., Waltham, MA, 1992.
53. Worth, G.A. "The Energetics of Nucleotide Binding to Ras Proteins." D.Phil. Thesis, Oxford University, 1992.
54. Nakagawa, S., Yu, H.-A., Karplus, M., Umeyama, H. Active site dynamics of acyl-chymotrypsin. Proteins 16: 172-194, 1993.
55. Brooks, C.L. III, Karplus, M. Solvent effects on protein motion and protein effects on solvent motion: Dynamics of the active site of lysozyme. J. Mol. Biol. 208:159-181, 1989.
56. Levine, R.D., Bernstein, R.B. "Molecular Reaction Dynamics and Chemical Reactivity." New York: Oxford University Press, 1987.
57. Wang, I.S.Y., Karplus, M. Dynamics of organic reactions. J. Am. Chem. Soc. 95:8160-8164, 1973.
58. Rossky, P.J., Simon, J.D. Dynamics of chemical processes in polar solvents. Nature 370:263-269, 1994.
59. Mulholland, A.J., Karplus, M. Simulations of enzymic reactions. Biochem. Soc. Trans. 24:247-254, 1996.
60. McCammon, J.A., Harvey, S.C. "Dynamics of Proteins and Nucleic Acids." Cambridge, U.K.: Cambridge University Press, 1987.
61. Brooks, C.L., III, Karplus, M., Pettitt, B.M. "Proteins: A Theoretical Perspective of Dynamics, Structure and Thermodynamics." New York: Wiley, 1988.
62. Mulholland, A.J. Richards, W.G. Studies on the reaction mechanism of citrate synthase. FASEB Journal, 10:3-4, 1996.
63. Mulholland, A.J., Richards, W.G. A comparison of semiempirical and ab initio transition states for HF elimination in unimolecular decompositions. Int. J. Quantum Chem. 51:161-172, 1994.
64. Mulholland, A.J. "Computer Simulation of Enzyme Mechanisms." D. Phil. Thesis, Oxford University, 1995.
65. Zheng, Y.-J., Merz, K.M. Jr. Study of hydrogen bonding interactions relevant to biomolecular structure and function. J. Comp. Chem. 13:1151-1169, 1992.
66. Stewart, J.J.P. "MOPAC 93.00 Manual." Tokyo: Fujitsu Ltd. 1993.
67. McDonald, I.K.M., Thornton, J.M. The application of hydrogen bonding analysis in x-ray crystallography to help orientate asparagine, glutamine and histidine side chains. Prot. Eng. 8:217-224, 1994.
68. Warshel, A., Russell, S.T. Calculations of electrostatic interactions in biological systems and in solutions. Q. Rev. Biophys. 17:283-422, 1984.
69. a's of ionizable groups in proteins: Atomic detail from a continuum electrostatic model. Biochemistry 29:10219-10225, 1990.
70. Honig, B., Nicholls, A. Classical electrostatics in biology and chemistry. Science 268:1144-1149, 1995.
71. Antosiewicz, J., McCammon, J.A., Gilson, M.K. Prediction of pH-dependent properties of proteins. J. Mol. Biol. 238:415-436, 1994.
72. Nicholls, A., Sharp, K.A., Honig, B. DelPhi 3.0. New York: Columbia University, 1990.
73. Donald, L.J., Duckworth, H.W. Expression and base sequence of the citrate synthase gene of the Acinetobacter anitratum. Biochem. Cell Biol. 65:930-938, 1987.
74. Sutherland, K.J., Henneke, C.M., Towner, P., Hough, D.W., Danson, M.J. Citrate synthase from the thermophilic archaebacterium Thermoplasma acidophilum: Cloning and sequencing of the gene. Eur. J. Biochem. 194:839-844, 1990.
75. Warshel, A. "Computer Modeling of Chemical Reactions in Enzymes and Solutions." New York: Wiley, 1991.
76. Gao, J., Mammen, M., Whitesides, G.M. Evaluating electrostatic contributions to binding with the use of protein charge ladders. Science 272:535-537, 1996.
77. Derewanda, Z.S., Derewenda, U., Kobos, P.M. (His)Ce-H⋯O=C< hydrogen bond in the active sites of serine hydrolases. J. Mol. Biol. 241:83-93, 1994.
78. Bachovchin, W.W. Confirmation of the assignment of the low-field proton resonance of serine proteases by using specifically nitrogen-15 labeled enzyme. Proc. Natl. Acad. Sci. USA 82:7948-7951, 1985.
79. Fersht, A. "Enzyme Structure and Mechanism," 2nd Ed. New York: W.H. Freeman. 1985.
80. Warshel, A., Náray-Szabó, G., Sussman, F., Hwang, J.-K. How do serine proteases really work? Biochemistry 28: 3629-3637, 1989.
81. Kosicki, G.W., Srere, P.A. Kinetic studies on the citrate-condensing enzyme. J. Biol. Chem. 236:2560-2565, 1961.
82. Amyes, T.L., Richard, J.P. Generation and stability of a simple thiol ester enolate in aqueous solution. J. Am. Chem. Soc. 114:10297-10302, 1992.
83. Knowles, J.R. To build an enzyme . . . Phil. Trans. R. Soc. Lond. B 332:115-121, 1991.
84. Chiang, Y., Kresge, A.J. Enols and other reactive species. Science 253:395-400, 1991.
85. Wilde, J., Lill, U., Eggerer, H. On the action of carboxy groups in the citrate synthase reaction. Biol. Chem. Hoppe-Seyler 371:707-713, 1990.
86. Cleland, W.W. Low-barrier hydrogen bonds and low fractionation factor bases in enzymatic reactions. Biochemistry 31:317-319, 1992.
87. 5-3-ketosteroid isomerase. Biochemistry 34:426-434, 1995.
88. Frey, P.A., Whitt, S.A., Tobin, J.B. A low-barrier hydrogen bond in the catalytic triad of serine proteases. Science 264:1927-1930, 1994.
89. Warshel, A., Papazyan, A., Kollman, P.A. On low-barrier hydrogen bonds and enzyme catalysis. Science 269:102-103, 1995.
90. Scheiner, S., Kar, T. The nonexistence of specially stabilized hydrogen bonds in enzymes. J. Am. Chem. Soc. 117: 6970-6975, 1995.
91. Guthrie, J.P., Kluger, R. Electrostatic stabilization can explain the unexpected acidity of carbon acids in enzyme-catalyzed reactions. J. Am. Chem. Soc. 115:11569-11572, 1993.
92. Yadav, A., Jackson, R.M., Holbrook, J.J., Warshel, A. Role of solvent reorganization energies in the catalytic activity of enzymes. J. Am. Chem. Soc. 113:4800-4805, 1991.
93. Warshel, A. Energetics of enzyme catalysis. Proc. Natl. Acad. Sci. USA 75:5250-5254, 1978.
94. Saunders, W.H. Jr. Ab initio Investigation of the acetaldehyde-to-acetaldehyde enolate proton transfer. J. Am. Chem. Soc. 116:5400-5404, 1994.
95. 5-steroid isomerase using the D38E and D38N mutants: The energetic basis for catalysis. Biochemistry 33:12172-12183, 1994.
96. - bonds: Gas-phase solvation and clustering of alkoxide and carboxylate anions. J. Am. Chem. Soc. 108:7525-7529, 1986.
97. Fersht, A.R., Shi, J.-P., Knill-Jones, J., Lowe, D.M., Wilkinson, A.J., Blow, D.M., Brick, P., Carter, P., Waye, M.Y., Winter, G. Hydrogen bonding and biological specificity analysed by protein engineering. Nature 314:235-233, 1985.
98. Albery, W.J., Knowles, J.R. Evolution of enzyme function and the development of catalytic efficiency. Biochemistry 15:5631-5640, 1976.
99. Kolb, M., Thiel, W. Beyond the MNDO model: Methodical considerations and numerical results. J. Comp. Chem. 14:775-789, 1993.
100. Dewar, M.J.S., Dieter, K.M. Mechanism of the chain extension step in the biosynthesis of fatty acids. Biochemistry 27:3302-3308, 1988.
101. Albery, W.J. The application of the Marcus relation to reactions in solution. Annu. Rev. Phys. Chem. 31:227-263, 1980.
102. Williams, I.H. Interplay of theory and experiment in the determination of transition-state structure. Chem. Soc. Rev. 22:277-283, 1993.