Substrate polarization in enzyme catalysis: QM/MM analysis of the effect of oxaloacetate polarization on acetyl-CoA enolization in citrate synthase

Proteins: Structure, Function and Genetics

Volumn 69, Issue 3, 2007, Pages 521-535

  Van Der Kamp, Marc W ^a   Perruccio, Francesca ^a,b   Mulholland, Adrian J ^a,c  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^c Cantock's Close   (United Kingdom)

Author keywords

AM1; B3LYP; CHARMM; Dynamics; Enolate; Free energy; Intermediate stabilization

Indexed keywords

ACETYL COENZYME A; CARBONYL DERIVATIVE; CITRATE SYNTHASE; CITRIC ACID; OXALOACETIC ACID;

ARTICLE; BIOTRANSFORMATION; CHEMICAL REACTION; CHICKEN; ENERGY TRANSFER; ENOLIZATION; ENZYME ACTIVE SITE; ENZYME MECHANISM; HYDROGEN BOND; HYDROLYSIS; MOLECULAR INTERACTION; MOLECULAR MECHANICS; MOLECULAR STABILITY; POLARIZATION; PRIORITY JOURNAL; QUANTUM MECHANICS; SIMULATION; SWINE;

ACETYL COENZYME A; ANIMALS; CATALYSIS; CHICKENS; CITRATE (SI)-SYNTHASE; ELECTROCHEMISTRY; GASES; HYDROGEN BONDING; MODELS, MOLECULAR; OXALOACETATE; PROTONS; QUANTUM THEORY; SOLUTIONS; THERMODYNAMICS; WATER;

EID: 35449000157     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.21482     Document Type: Article

References (67)

1. Breuer M, Hauer B. Carbon-carbon coupling in biotransformation. Curr Opin Biotechnol 2003;14:570-576.
2. Sukumaran J, Hanefeld U. Enantioselective C-C bond synthesis catalysed by enzymes. Chem Soc Rev 2005;34:530-542.
3. Bugg T. An introduction to enzyme and coenzyme chemistry. Oxford: Blackwell Science; 1997.
4. Bayliss SWM. The nature of enzyme action. London: Longmans Green; 1925.
5. Quastel JH. Dehydrogenations produced by resting bacteria. IV. A theory of the mechanism of oxidations and reductions in vivo. Biochem J 1926;20:166-194.
6. Belasco JG, Knowles JR. Direct observation of substrate distortion by triosephosphate isomerase using Fourier transform infrared spectroscopy. Biochemistry 1980;19:472-477.
7. Warshel A, Sharma PK, Kato M, Xiang Y, Liu HB, Olsson MHM. Electrostatic basis for enzyme catalysis. Chem Rev 2006;106:3210-3235.
8. Fersht A. Enzyme structure and mechanism, 2 ed. New York: WH. Freeman; 1984. pp 311-346.
9. Haldane JBS. Enzymes. London: Longmans Green; 1930. p 182.
10. Garcia-Viloca M, Gao J, Karplus M, Truhlar DG. How enzymes work: analysis by modern rate theory and computer simulations. Science 2004;303:186-195.
11. Warshel A, Florían J. Computer simulations of enzyme catalysis: finding out what has been optimized by evolution. Proc Natl Acad Sci USA 1998;95:5950-5955.
12. Mulholland AJ. Modelling enzyme reaction mechanisms, specificity and catalysis. Drug Discov Today 2005;10:1393-1402.
13. Kurz LC, Ackerman JJH, Drysdale GR. Evidence from C-13 NMR for polarization of the carbonyl of oxaloacetate in the active-site of citrate synthase. Biochemistry 1985;24:452-457.
14. Kurz LC, Drysdale GR. Evidence from Fourier-transform infrared-spectroscopy for polarization of the carbonyl of oxaloacetate in the active-site of citrate synthase. Biochemistry 1987;26:2623-2627.
15. Evans CT, Kurz LC, Remington SJ, Srere PA. Active site mutants of pig citrate synthase: effects of mutations on the enzyme catalytic and structural properties. Biochemistry 1996;35:10661-10672.
16. Donini O, Darden T, Kollman PA. QM-FE calculations of aliphatic hydrogen abstraction in citrate synthase and in solution: reproduction of the effect of enzyme catalysis and demonstration that an enolate rather than an enol is formed. J Am Chem Soc 2000; 122:12270-12280.
17. Karpusas M, Holland D, Remington SJ. 1.9-Å structures of ternary complexes of citrate synthase with D-malate and L-malate - mechanistic implications. Biochemistry 1991;30:6024-6031.
18. Kurz LC, Nakra T, Stein R, Plungkhen W, Riley M, Hsu F, Drysdale GR. Effects of changes in three catalytic residues on the relative stabilities of some of the intermediates and transition states in the citrate synthase reaction. Biochemistry 1998;37:9724-9737.
19. Kurz LC, Fite B, Jean J, Park J, Erpelding T, Callis P. Photophysics of tryptophan fluorescence: link with the catalytic strategy of the citrate synthase from Thermoplasma acidophilum. Biochemistry 2005; 44:1394-1413.
20. Mulholland AJ, Lyne PD, Karplus M. Ab initio QM/MM study of the citrate synthase mechanism. A low-barrier hydrogen bond is not involved. J Am Chem Soc 2000;122:534-535.
21. Mulholland AJ, Richards WG. Acetyl-CoA enolization in citrate synthase: a quantum mechanical/molecular mechanical (QM/MM) study. Proteins: Struct Funct Genet 1997;27:9-25.
22. Mulholland AJ, Richards WG. Modeling enzyme reaction intermediates and transition states: citrate synthase. J Phys Chem B 1998; 102:6635-6646.
23. Remington SJ. Structure and mechanism of citrate synthase. Curr Top Cell Regul 1992;33:209-229.
24. Yang W, Drueckhammer DG. Computational study of the citrate synthase catalyzed deprotonation of acetyl-coenzyme a and fluoroacetyl-coenzyme A: demonstration of a layered quantum mechanical approach. J Phys Chem B 2003;107:5986-5994.
25. Mulholland AJ, Richards WG. Modeling the citrate synthase reaction: QM/MM and small model calculations. In: Truhlar DG, Morokuma K, editors. Transition state modeling for catalysis (ACS Symposium Series, Vol. 721). Washington, DC: American Chemical Society; 1999. pp 448-461.
26. Usher KC, Remington SJ, Martin DP, Drueckhammer DG. A very short hydrogen bond provides only moderate stabilization of an enzyme-inhibitor complex of citrate synthase. Biochemistry 1994;33: 7753-7759.
27. Kollmann-Koch A, Eggerer H. Ligand-induced conformational changes of citrate synthase studied with the fluorescent probe 8-anilinonaphthalene 1-sulfonate. Eur J Biochem 1989;185:441-447.
28. Weidman SW, Drysdale GR, Mildvan AS. Interaction of a spin-labeled analog of acetyl coenzyme A with citrate synthase. Paramagnetic resonance and proton relaxation rate studies of binary and ternary complexes. Biochemistry 1973;12:1874-1883.
29. Mulholland AJ, Richards WG. Calculations on the substrates of citrate synthase. I. Oxaloacetate. J Mol Struct (THEOCHEM) 1998; 429:13-21.
30. Eggerer H. Zum Mechanismus der biologischen Umwandlung von Citronensaure. VI. Citrat-Synthase ist eine Acetyl-Co A Enolase. Biochem Z 1965;343:111-138.
31. Bové J, Martin RO, Ingraham LL, Stumpf PK. Studies of the mechanism of the condensing enzyme. J Biol Chem 1959;234:999-1003.
32. Wlassics ID, Anderson VE. Citrate synthase stabilizes the enethiolate of acetyldithio coenzyme-A. Biochemistry 1989;28:1627-1633.
33. Mulholland AJ. Ab initio QM/MM calculations on the citrate synthase reaction. J Mol Graph Model 1998;16:271-272.
34. Thibblin A, Jencks WP. Unstable carbanions - general acid catalysis of the cleavage of 1-phenylcyclopropanol and 1-phenyl-2-arylcyclopropanol anions. J Am Chem Soc 1979;101:4963-4973.
35. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The protein data bank. Nucleic Acids Res 2000;28:235-242.
36. Perruccio F. Molecular modelling of the citrate synthase reaction mechanism, PhD Thesis. Bristol: Univeristy of Bristol; 2002.
37. Brooks CL, Karplus M. Deformable stochastic boundaries in molecular-dynamics. J Chem Phys 1983;79:6312-6325.
38. Brooks CL, Karplus M. Solvent effects on protein motion and protein effects on solvent motion - dynamics of the active-site region of lysozyme. J Mol Biol 1989;208:159-181.
39. Ryckaert JP, Cicotti G, Berendsen HJC. Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 1977;23:324-341.
40. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys 1983;79:926-935.
41. MacKerell AD, Jr, Banavali N, Foloppe N. Development and current status of the CHARMM force field for nucleic acids. Biopolymers 2000;56:257-265.
42. MacKerell AD, Jr, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 1998;102: 3586-3616.
43. Bayly CI, Cieplak P, Cornell WD, Kollman PA. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges - the RESP model. J Phys Chem 1993;97:10269-10280.
44. Field MJ, Bash PA, Karplus M. A combined quantum-mechanical and molecular mechanical potential for molecular-dynamics simulations. J Comput Chem 1990;11:700-733.
45. Reuter N, Dejaegere A, Maigret B, Karplus M. Frontier bonds in QM/MM methods: a comparison of different approaches. J Phys Chem A 2000;104:1720-1735.
46. Ridder LO, Rietjens IMCM, Vervoort J, Mulholland AJM. Quantum mechanical/molecular mechanical free energy simulations of the glutathione S-transferase (M1-1) reaction with phenanthrene 9,10-Oxide. J Am Chem Soc 2002;124:9926-9936.
47. Bartels C, Karplus M. Multidimensional adaptive umbrella sampling: applications to main chain and side chain peptide conformations. J Comput Chem 1997;18:1450-1462.
48. Kumar S, Bouzida D, Swendsen RH, Kollman PA, Rosenberg JM. The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. J Comput Chem 1992;13: 1011-1021.
49. Jaguar 5.0. Portland, OR: Schrodinger, LLC; 2002.
50. Ponder JW. TINKER: software tools for molecular design, V 4.0. Saint Louis, MO: Washington University School of Medicine; 2003.
51. Harvey JN. Spin-forbidden CO ligand recombination in myoglobin. Faraday Discuss 2004;127:165-177.
52. Mulliken RS. Electronic population analysis on LCAOMO molecular wave functions. I. J Chem Phys 1955;23:1833-1840.
53. Chirlian LE, Francl MM. Atomic charges derived from electrostatic potentials: a detailed study. J Comput Chem 1987;8:894-905.
54. Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Bohmann JA, Morales CM, Weinhold F. NBO 5.0. Madison, WI: Theoretical Chemistry Institute, University of Wisconsin; 2001.
55. Pigache A, Cieplak P, Dupradeau F-Y. Automatic and highly reproducible RESP and ESP charge derivation: application to the development of programs RED and X RED. Anaheim, CA: American Chemical Society; 2004.
56. Wang JM, Wolf RM, Caldwell JW, Kollman PA, Case DA. Development and testing of a general amber force field. J Comput Chem 2004;25:1157-1174.
57. Alter GM, Casazza JP, Wang Z, Nemeth P, Srere PA, Evans CT. Mutation of essential catalytic residues in pig citrate synthase. Biochemistry 1990;29:7557-7563.
58. Mulholland AJ, Richards WG. Studies on the reaction mechanism of citrate synthase. FASEB J 1996;10:C3.
59. Svensson M, Humbel S, Froese RDJ, Matsubara T, Sieber S, Morokuma K. ONIOM: a multi-layered integrated MO + MM method for geometry optimizations and single point energy predictions. A test for Diels-Alder reactions and Pt(P(t-Bu)3)2 + H2 oxidative addition. J Phys Chem 1996;100:19357-19363.
60. Stanton RVPM, Bakowies D, Kollman PA. Combined ab initio and free energy calculations to study reactions in enzymes and solution: amide hydrolysis in trypsin and aqueous solution. J Am Chem Soc 1998;120:3448-3457.
61. Zheng Y-J, Merz KM, Jr. Study of hydrogen bonding interactions relevant to biomolecular structure and function. J Comput Chem 1992;13:1151-1169.
62. Masgrau L, Basran J, Hothi P, Sutcliffe MJ, Scrutton NS. Hydrogen tunneling in quinoproteins. Arch Biochem Biophys 2004;428:41-51.
63. Masgrau L, Roujeinikova A, Johannissen LO, Hothi P, Basran J, Ranaghan KE, Mulholland AJ, Sutcliffe MJ, Scrutton NS, Leys D. Atomic description of an enzyme reaction dominated by proton tunneling. Science 2006;312:237-241.
64. Kosicki G, Srere PA. Deuterium istopope rate effects with citrate-condensing enzyme. J Biol Chem 1961;236:2566.
65. Lenz H, Buckel W, Wunderwa P, Biederma G, Buschmei V, Eggerer H, Cornfort JW, Redmond JW, Mallaby R. Stereochemistry of Si-citrate synthase and ATP-citrate-lyase reactions. Eur J Biochem 1971; 24:207-215.
66. Warshel A, Sharma PK, Chu ZT, Åqvist J. Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase. Biochemistry 2007;46:1466-1476.
67. Van der Kamp MW, Perruccio F, Mulholland AJ. Ab initio QM/MM modelling of acetyl-CoA deprotonation in the enzyme citrate synthase. J Mol Graph Model 2007. doi:10.1016/j.jmgm.2007.04.002.