How is acetylcholinesterase phosphonylated by Soman? An ab initio QM/MM molecular dynamics study

Journal of Physical Chemistry A

Volumn 118, Issue 39, 2014, Pages 9132-9139

  Sirin, Gulseher Sarah ^a   Zhang, Yingkai ^a,b  

^a NEW YORK UNIVERSITY   (United States)

^b NEW YORK UNIVERSITY SHANGHAI   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AB INITIO; ACETYLCHOLINESTERASE;

ACETYLCHOLINESTERASE; FLUORINE; PHOSPHONIC ACID DERIVATIVE; SERINE; SOMAN;

CHEMICAL STRUCTURE; CHEMISTRY; MOLECULAR DYNAMICS; QUANTUM THEORY;

ACETYLCHOLINESTERASE; FLUORINE; MOLECULAR DYNAMICS SIMULATION; MOLECULAR STRUCTURE; ORGANOPHOSPHONATES; QUANTUM THEORY; SERINE; SOMAN;

EID: 84907701951     PISSN: 10895639     EISSN: 15205215     Source Type: Journal    
DOI: 10.1021/jp502712d     Document Type: Article

References (91)

1. Rosenberry, T. L. Acetylcholinesterase Adv. Enzymol. Relat. Areas Mol. Biol. 2006, 43, 103-218
2. Quinn, D. M. Acetylcholinesterase: Enzyme Structure, Reaction Dynamics, and Virtual Transition States Chem. Rev. 1987, 87, 955-979
3. Sussman, J. L.; Harel, M.; Frolow, F.; Oefner, C.; Goldman, A.; Toker, L.; Silman, I. Atomic Structure of Acetylcholinesterase from Torpedo Californica: A Prototypic Acetylcholine-Binding Protein Science 1991, 253, 872-879
4. Sanson, B.; Nachon, F.; Colletier, J.-P.; Froment, M.-T.; Toker, L.; Greenblatt, H. M.; Sussman, J. L.; Ashani, Y.; Masson, P.; Silman, I. Crystallographic Snapshots of Nonaged and Aged Conjugates of Soman with Acetylcholinesterase, and of a Ternary Complex of the Aged Conjugate with Pralidoxime J. Med. Chem. 2009, 52, 7593-7603
5. Harel, M.; Quinn, D. M.; Nair, H. K.; Silman, I.; Sussman, J. L. The X-Ray Structure of a Transition State Analog Complex Reveals the Molecular Origins of the Catalytic Power and Substrate Specificity of Acetylcholinesterase J. Am. Chem. Soc. 1996, 118, 2340-2346
6. Fuxreiter, M.; Warshel, A. Origin of the Catalytic Power of Acetylcholinesterase: Computer Simulation Studies J. Am. Chem. Soc. 1998, 120, 183-194
7. Zhang, Y.; Kua, J.; McCammon, J. A. Role of the Catalytic Triad and Oxyanion Hole in Acetylcholinesterase Catalysis: An Ab Initio QM/MM Study J. Am. Chem. Soc. 2002, 124, 10572-10577
8. Malany, S.; Sawai, M.; Sikorski, R. S.; Seravalli, J.; Quinn, D. M.; Radic, Z.; Taylor, P.; Kronman, C.; Velan, B.; Shafferman, A. Transition State Structure and Rate Determination for the Acylation Stage of Acetylcholinesterase Catalyzed Hydrolysis of (Acetylthio) Choline J. Am. Chem. Soc. 2000, 122, 2981-2987
9. Manojkumar, T.; Cui, C.; Kim, K. S. Theoretical Insights into the Mechanism of Acetylcholinesterase, Catalyzed Acylation of Acetylcholine J. Comput. Chem. 2005, 26, 606-611
10. Massiah, M. A.; Viragh, C.; Reddy, P. M.; Kovach, I. M.; Johnson, J.; Rosenberry, T. L.; Mildvan, A. S. Short, Strong Hydrogen Bonds at the Active Site of Human Acetylcholinesterase: Proton NMR Studies Biochemistry 2001, 40, 5682-5690
11. Nemukhin, A. V.; Lushchekina, S. V.; Bochenkova, A. V.; Golubeva, A. A.; Varfolomeev, S. D. Characterization of a Complete Cycle of Acetylcholinesterase Catalysis by Ab Initio QM/MM Modeling J. Mol. Model. 2008, 14, 409-416
12. Vagedes, P.; Rabenstein, B.; Aqvist, J.; Marelius, J.; Knapp, E. W. The Deacylation Step of Acetylcholinesterase: Computer Simulation Studies J. Am. Chem. Soc. 2000, 122, 12254-12262
13. Vasilyev, V. Tetrahedral Intermediate Formation in the Acylation Step of Acetylcholinesterases. A Combined Quantum Chemical and Molecular Mechanical Model J. Mol. Struct.: THEOCHEM 1994, 304, 129-141
14. Zhou, Y.; Wang, S.; Zhang, Y. Catalytic Reaction Mechanism of Acetylcholinesterase Determined by Born Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations J. Phys. Chem. B 2010, 114, 8817-8825
15. Wlodek, S. T.; Antosiewicz, J.; Briggs, J. M. On the Mechanism of Acetylcholinesterase Action: The Electrostatically Induced Acceleration of the Catalytic Acylation Step J. Am. Chem. Soc. 1997, 119, 8159-8165
16. Wang, B.; Wang, H.; Wei, Z.; Song, Y.; Zhang, L.; Chen, H. Efficacy and Safety of Natural Acetylcholinesterase Inhibitor Huperzine a in the Treatment of Alzheimer's Disease: An Updated Meta-Analysis J. Neural Transm. 2009, 116, 457-465
17. Ordentlich, A.; Barak, D.; Kronman, C.; Ariel, N.; Segall, Y.; Velan, B.; Shafferman, A. The Architecture of Human Acetylcholinesterase Active Center Probed by Interactions with Selected Organophosphate Inhibitors J. Biol. Chem. 1996, 271, 11953-11962
18. Birks, J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database of Systematic Reviews 2006, Issue 1, Art. No.: CD005593. DOI: 10.1002/14651858.CD005593.
19. Gonçalves, A. S.; França, T. C. C.; Figueroa-Villar, J. D.; Pascutti, P. G. Molecular Dynamics Simulations and QM/MM Studies of the Reactivation by 2-Pam of Tabun Inhibited Human Acethylcolinesterase J. Braz. Chem. Soc. 2011, 22, 155-165
20. Costa, L.; Giordano, G.; Guizzetti, M.; Vitalone, A. Neurotoxicity of Pesticides: A Brief Review Front. Biosci. 2008, 13, 1240
21. Pope, C. N. Organophosphorus Pesticides: Do They All Have the Same Mechanism of Toxicity? J. Toxicol. Environ. Health, Part B 1999, 2, 161-181
22. Bajgar, J. Organophosphates, Nerve Agent Poisoning: Mechanism of Action, Diagnosis, Prophylaxis, and Treatment Adv. Clin. Chem. 2004, 38, 151-216
23. Holstege, C. P.; Kirk, M.; Sidell, F. R. Chemical Warfare: Nerve Agent Poisoning Crit. Care Clin. 1997, 13, 923-942
24. Smart, J. K. History of Chemical and Biological Warfare: An American Perspective. Medical Aspects of Chemical and Biological Warfare; Office of the Surgeon General: Washington, DC, 1997; pp 9-86.
25. Okudera, H.; Morita, H.; Iwashita, T.; Shibata, T.; Otagiri, T.; Kobayashi, S.; Yanagisawa, N. Unexpected Nerve Gas Exposure in the City of Matsumoto: Report of Rescue Activity in the First Sarin Gas Terrorism Am. J. Emerg. Med. 1997, 15, 527-528
26. Hay, A.; Roberts, G. The Use of Poison Gas against the Iraqi Kurds: Analysis of Bomb Fragments, Soil, and Wool Samples JAMA, J. Am. Med. Assoc. 1990, 263, 1065-1066
27. Marrs, T. C. Organophosphate Poisoning Pharmacol. Ther. 1993, 58, 51-66
28. Gupta, R. C. Toxicology of Organophosphate and Carbamate Compounds; Academic Press, 2006.
29. Fest, C.; Schmidt, K. J. The Chemistry of Organophosphorus Pesticides; Springer-Verlag: Berlin, 1982; Vol. 352.
30. Eddleston, M.; Buckley, N. A.; Eyer, P.; Dawson, A. H. Management of Acute Organophosphorus Pesticide Poisoning Lancet 2008, 371, 597-607
31. Shafferman, A.; Ordentlich, A.; Barak, D.; Stein, D.; Ariel, N.; Velan, B. Aging of Phosphylated Human Acetylcholinesterase: Catalytic Processes Mediated by Aromatic and Polar Residues of the Active Centre Biochem. J. 1996, 318, 833-840
32. Kwasnieski, O. l.; Verdier, L.; Malacria, M.; Derat, E. Fixation of the Two Tabun Isomers in Acetylcholinesterase: A QM/MM Study J. Phys. Chem. B 2009, 113, 10001-10007
33. Beck, J. M.; Hadad, C. M. Reaction Profiles of the Interaction between Sarin and Acetylcholinesterase and the S203c Mutant: Model Nucleophiles and QM/MM Potential Energy Surfaces Chem.-Biol. Interact. 2010, 187, 220-224
34. Wang, J.; Gu, J.; Leszczynski, J. Phosphonylation Mechanisms of Sarin and Acetylcholinesterase: A Model Dft Study J. Phys. Chem. B 2006, 110, 7567-7573
35. Wang, J.; Gu, J.; Leszczynski, J. Theoretical Modeling Study for the Phosphonylation Mechanisms of the Catalytic Triad of Acetylcholinesterase by Sarin J. Phys. Chem. B 2008, 112, 3485-3494
36. Bencsura, A.; Enyedy, I.; Kovach, I. M. Origins and Diversity of the Aging Reaction in Phosphonate Adducts of Serine Hydrolase Enzymes: What Characteristics of the Active Site Do They Probe? Biochemistry 1995, 34, 8989-8999
37. Sterri, S. H.; Fonnum, F. Carboxylesterases in Guinea-Pig Plasma and Liver: Tissue Specific Reactivation by Diacetylmonoxime after Soman Inhibition in Vitro Biochem. Pharmacol. 1987, 36, 3937-3942
38. Kovach, I. M. Structure and Dynamics of Serine Hydrolase-Organophosphate Adducts J. Enzyme Inhib. Med. Chem. 1988, 2, 199-208
39. George, K. M.; Schule, T.; Sandoval, L. E.; Jennings, L. L.; Taylor, P.; Thompson, C. M. Differentiation between Acetylcholinesterase and the Organophosphate-Inhibited Form Using Antibodies and the Correlation of Antibody Recognition with Reactivation Mechanism and Rate J. Biol. Chem. 2003, 278, 45512-45518
40. Larsson, L. The Alkaline Hydrolysis of Isopropoxy-Methyl-Phosphoryl Fluoride (Sarin) and Some Analogues Acta Chem. Scand. 1957, 11, 1131-1142
41. Zheng, F.; Zhan, C. G.; Ornstein, R. L. Theoretical Studies of Reaction Pathways and Energy Barriers for Alkaline Hydrolysis of Phosphotriesterase Substrates Paraoxon and Related Toxic Phosphofluoridate Nerve Agents J. Chem. Soc., Perkin Trans. 1 2001, 2355-2363
42. Florian, J.; Warshel, A. Phosphate Ester Hydrolysis in Aqueous Solution: Associative Versus Dissociative Mechanisms J. Phys. Chem. B 1998, 102, 719-734
43. J. Seckute, J.; Menke, J. L.; Emnett, R. J.; Patterson, E. V.; Cramer, C. J. Ab Initio Molecular Orbital and Density Functional Studies on the Solvolysis of Sarin and O, S-Dimethyl Methylphosphonothiolate, a VX-Like Compound J. Org. Chem. 2005, 70, 8649-8660
44. Aqvist, J.; Kolmodin, K.; Florian, J.; Warshel, A. Mechanistic Alternatives in Phosphate Monoester Hydrolysis: What Conclusions Can Be Drawn from Available Experimental Data? Chem. Biol. 1999, 6, R71-R80
45. Hurley, M.; Wright, J.; Lushington, G.; White, W. Quantum Mechanics and Mixed Quantum Mechanics/Molecular Mechanics Simulations of Model Nerve Agents with Acetylcholinesterase Theor. Chem. Acc. 2003, 109, 160-168
46. Ding, J.; Yao, Y.; Zhang, H.; Li, Z. S. Phosphonylation and Aging Mechanisms of Mipafox and Butyrylcholinesterase: A Theoretical Study Chin. Sci. Bull. 2012, 57, 4453-4461
47. Qian, N.; Kovach, I. M. Key Active Site Residues in the Inhibition of Acetylcholinesterases by Soman FEBS Lett. 1993, 336, 263-266
48. Millard, C. B.; Kryger, G.; Ordentlich, A.; Greenblatt, H. M.; Harel, M.; Raves, M. L.; Segall, Y.; Barak, D.; Shafferman, A.; Silman, I. Crystal Structures of Aged Phosphonylated Acetylcholinesterase: Nerve Agent Reaction Products at the Atomic Level Biochemistry 1999, 38, 7032-7039
49. Zhou, Y.; Zhang, Y. Serine Protease Acylation Proceeds with a Subtle Re-Orientation of the Histidine Ring at the Tetrahedral Intermediate Chem. Commun. 2011, 47, 1577-1579
50. Hu, H.; Yang, W. Free Energies of Chemical Reactions in Solution and in Enzymes with Ab Initio Quantum Mechanics/Molecular Mechanics Methods Annu. Rev. Phys. Chem. 2008, 59, 573-601
51. Hu, P.; Wang, S.; Zhang, Y. Highly Dissociative and Concerted Mechanism for the Nicotinamide Cleavage Reaction in Sir2tm Enzyme Suggested by Ab Initio QM/MM Molecular Dynamics Simulations J. Am. Chem. Soc. 2008, 130, 16721-16728
52. Hu, P.; Wang, S.; Zhang, Y. How Do Set-Domain Protein Lysine Methyltransferases Achieve the Methylation State Specificity? Revisited by Ab Initio QM/MM Molecular Dynamics Simulations J. Am. Chem. Soc. 2008, 130, 3806-3813
53. Ke, Z.; Guo, H.; Xie, D.; Wang, S.; Zhang, Y. Ab Initio QM/MM Free-Energy Studies of Arginine Deiminase Catalysis: The Protonation State of the Cys Nucleophile J. Phys. Chem. B 2011, 115, 3725-3733
54. Ke, Z.; Smith, G. K.; Zhang, Y.; Guo, H. Molecular Mechanism for Eliminylation, a Newly Discovered Post-Translational Modification J. Am. Chem. Soc. 2011, 133, 11103-11105
55. Ke, Z.; Zhou, Y.; Hu, P.; Wang, S.; Xie, D.; Zhang, Y. Active Site Cysteine Is Protonated in the Pad4Michaelis Complex: Evidence from Born, Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations J. Phys. Chem. B 2009, 113, 12750-12758
56. Liu, J.; Zhang, Y.; Zhan, C. G. Reaction Pathway and Free-Energy Barrier for Reactivation of Dimethylphosphoryl-Inhibited Human Acetylcholinesterase J. Phys. Chem. B 2009, 113, 16226-16236
57. Wu, R.; Hu, P.; Wang, S.; Cao, Z.; Zhang, Y. Flexibility of Catalytic Zinc Coordination in Thermolysin and HDAC8: A Born,Oppenheimer Ab Initio QM/MM Molecular Dynamics Study J. Chem. Theory Comput. 2009, 6, 337-343
58. Wu, R.; Wang, S.; Zhou, N.; Cao, Z.; Zhang, Y. A Proton-Shuttle Reaction Mechanism for Histone Deacetylase 8 and the Catalytic Role of Metal Ions J. Am. Chem. Soc. 2010, 132, 9471-9479
59. Wu, R.; Lu, Z.; Cao, Z.; Zhang, Y. Zinc Chelation with Hydroxamate in Histone Deacetylases Modulated by Water Access to the Linker Binding Channel J. Am. Chem. Soc. 2011, 133, 6110-6113
60. Ke, Z.; Wang, S.; Xie, D.; Zhang, Y. Born, Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations of the Hydrolysis Reaction Catalyzed by Protein Arginine Deiminase 4 J. Phys. Chem. B 2009, 113, 16705-16710
61. Sirin, G. S.; Zhou, Y.; Lior-Hoffmann, L.; Wang, S.; Zhang, Y. Aging Mechanism of Soman Inhibited Acetylcholinesterase J. Phys. Chem. B 2012, 116, 12199-12207
62. Gordon, J. C.; Myers, J. B.; Folta, T.; Shoja, V.; Heath, L. S.; Onufriev, A. H++: A Server for Estimating Pkas and Adding Missing Hydrogens to Macromolecules Nucleic Acids Res. 2005, 33, W368-W371
63. Case, D. A.; Darden, T. A.; Cheatham, T. E.; Simmerling, C. L.; Wang, J.; Duke, R. E.; Luo, R.; Crowley, M.; Walker, R. C.; Zhang, W.; AMBER 11; University of California: San Francisco, CA, 2010.
64. Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and Testing of a General Amber Force Field J. Comput. Chem. 2004, 25, 1157-1174
65. Wang, J.; Wang, W.; Kollman, P. A.; Case, D. A. Automatic Atom Type and Bond Type Perception in Molecular Mechanical Calculations J. Mol. Graphics Modell. 2006, 25, 247-260
66. Hornak, V.; Abel, R.; Okur, A.; Strockbine, B.; Roitberg, A.; Simmerling, C. Comparison of Multiple Amber Force Fields and Development of Improved Protein Backbone Parameters Proteins: Struct., Funct., Bioinf. 2006, 65, 712-725
67. Wang, J.; Cieplak, P.; Kollman, P. A. How Well Does a Restrained Electrostatic Potential (RESP) Model Perform in Calculating Conformational Energies of Organic and Biological Molecules? J. Comput. Chem. 2000, 21, 1049-1074
68. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules J. Am. Chem. Soc. 1995, 117, 5179-5197
69. 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. 1983, 79, 926-935
70. Berendsen, H. J. C.; Postma, J. P. M.; Van Gunsteren, W. F.; DiNola, A.; Haak, J. Molecular Dynamics with Coupling to an External Bath J. Chem. Phys. 1984, 81, 3684-3690
71. Zhang, Y. Pseudobond Ab Initio QM/MM Approach and Its Applications to Enzyme Reactions Theor. Chem. Acc. 2006, 116, 43-50
72. Zhang, Y. Improved Pseudobonds for Combined Ab Initio Quantum Mechanical/Molecular Mechanical Methods J. Chem. Phys. 2005, 122, 024114-024120
73. Zhang, Y.; Lee, T. S.; Yang, W. A Pseudobond Approach to Combining Quantum Mechanical and Molecular Mechanical Methods J. Chem. Phys. 1999, 110, 46-54
74. Liu, H.; Zhang, Y.; Yang, W. How Is the Active Site of Enolase Organized to Catalyze Two Different Reaction Steps? J. Am. Chem. Soc. 2000, 122, 6560-6570
75. Zhang, Y.; Liu, H.; Yang, W. Free Energy Calculation on Enzyme Reactions with an Efficient Iterative Procedure to Determine Minimum Energy Paths on a Combined Ab Initio QM/MM Potential Energy Surface J. Chem. Phys. 2000, 112, 3483-3492
76. Beeman, D. Algorithms for Molecular Dynamics at Constant Temperature and Pressure J. Comput. Phys. 1976, 20, 130-136
77. Shao, Y.; Molnar, L. F.; Jung, Y.; Kussmann, J.; Ochsenfeld, C.; Brown, S. T.; Gilbert, A. T.; Slipchenko, L. V.; Levchenko, S. V.; O'Neill, D. P.; Q-Chem; Q-Chem, Inc.: Pittsburgh, PA, 2006.
78. Ponder, J. W. TINKER: Software Tools for Molecular Design. Washington University School of Medicine: Saint Louis, MO, 2004.
79. Warshel, A.; Levitt, M. Theoretical Studies of Enzymic Reactions: Dielectric, Electrostatic and Steric Stabilization of the Carbonium Ion in the Reaction of Lysozyme J. Mol. Biol. 1976, 103, 227-249
80. Singh, U. C.; Kollman, P. A. A Combined Ab Initio Quantum Mechanical and Molecular Mechanical Method for Carrying out Simulations on Complex Molecular Systems: Applications to the CH3Cl + Cl- Exchange Reaction and Gas Phase Protonation of Polyethers J. Comput. Chem. 1986, 7, 718-730
81. Adrian J, M. Modelling Enzyme Reaction Mechanisms, Specificity and Catalysis Drug Discovery Today 2005, 10, 1393-1402
82. Gao, J.; Truhlar, D. G. Quantum Mechanical Methods for Enzyme Kinetics Annu. Rev. Phys. Chem. 2002, 53, 467-505
83. Friesner, R. A.; Guallar, V. Ab Initio Quantum Chemical and Mixed Quantum Mechanics/Molecular Mechanics (QM/MM) Methods for Studying Enzymatic Catalysis Annu. Rev. Phys. Chem. 2005, 56, 389-427
84. Benoit, R. The Calculation of the Potential of Mean Force Using Computer Simulations Comput. Phys. Commun. 1995, 91, 275-282
85. Boczko, E. M.; Brooks, C. L. Constant-Temperature Free Energy Surfaces for Physical and Chemical Processes J. Phys. Chem. 1993, 97, 4509-4513
86. Patey, G.; Valleau, J. A Monte Carlo Method for Obtaining the Interionic Potential of Mean Force in Ionic Solution J. Chem. Phys. 1975, 63, 2334-2339
87. Souaille, M.; Roux, B. Extension to the Weighted Histogram Analysis Method: Combining Umbrella Sampling with Free Energy Calculations Comput. Phys. Commun. 2001, 135, 40-57
88. Kumar, S.; Rosenberg, J. M.; Bouzida, D.; Swendsen, R. H.; Kollman, P. A. The Weighted Histogram Analysis Method for Free Energy Calculations on Biomolecules. I. The Method J. Comput. Chem. 1992, 13, 1011-1021
89. Ferrenberg, A. M.; Swendsen, R. H. New Monte Carlo Technique for Studying Phase Transitions Phys. Rev. Lett. 1988, 61, 2635-2638
90. Mildvan, A. S. Mechanisms of Signaling and Related Enzymes Proteins: Struct., Funct., Bioinf. 1997, 29, 401-416
91. Pauling, L. The Nature of the Chemical Bond and the Structure of Molecules and Crystals: An Introduction to Modern Structural Chemistry. Cornell University Press, 1960; Vol. 18.