A QM/QM investigation of the hUNG2 reaction surface: The untold tale of a catalytic residue

Biochemistry

Volumn 50, Issue 19, 2011, Pages 4218-4227

  Przybylski, Jennifer L ^a   Wetmore, Stacey D ^a  

^a UNIVERSITY OF LETHBRIDGE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVE SITE; BASE EXCISION REPAIRS; BINDING ORIENTATION; CARBOXYLATE GROUPS; CATALYTIC RESIDUE; DEGLYCOSYLATION; ELECTROSTATIC STABILIZATION; EXPERIMENTAL DATA; GENERAL BASE; HYDROGEN BONDINGS; NEGATIVE CHARGE; POSITIVE CHARGES; PRIMARY FUNCTIONS; PROTONATION STATE; REACTION PATHWAYS; REACTION SURFACES; SUGAR MOIETY; TRANSITION STATE STABILIZATION; URACIL-DNA GLYCOSYLASE; WATER MOLECULE;

AMINO ACIDS; CARBOXYLATION; ENZYMES; MOLECULES; NUCLEIC ACIDS; QUANTUM CHEMISTRY; STABILIZATION; SUGARS;

SURFACE REACTIONS;

NUCLEOPHILE; UNCLASSIFIED DRUG; URACIL DNA GLYCOSIDASE; URACIL DNA GLYCOSIDASE 2; WATER;

ARTICLE; BINDING SITE; CATALYSIS; ENZYME CONFORMATION; ENZYME MECHANISM; ENZYME STABILITY; ENZYME STRUCTURE; HUMAN; HYDROGEN BOND; MUTATIONAL ANALYSIS; POINT MUTATION; PRIORITY JOURNAL; PROTON TRANSPORT;

ASPARAGINE; ASPARTIC ACID; CATALYSIS; CATALYTIC DOMAIN; COMPUTER SIMULATION; DNA MUTATIONAL ANALYSIS; GLUTAMIC ACID; HISTIDINE; HUMANS; MODELS, MOLECULAR; PROLINE; PROTONS; QUANTUM THEORY; STATIC ELECTRICITY; SURFACE PROPERTIES; URACIL-DNA GLYCOSIDASE; WATER;

EID: 79955826385     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi2003394     Document Type: Article

References (55)

1. Lindahl, T. (1974) An N-Glycosidase from Eschirichia coli that Releases Free Uracil from DNA Containing Deaminated Cytosine Residues Proc. Natl. Acad. Sci. U.S.A. 71, 3649-3653
2. Krokan, H. and Wittwer, C. U. (1981) Uracil DNA-Glycosylase from HeLa-Cells-General-Properties, Substrate-Specificity and Effect of Uracil Analogs Nucleic Acids Res. 9, 2599-2613
3. Kavli, B., Sundheim, O., Akbari, M., Otterlei, M., Nilsen, H., Skorpen, F., Aas, P. A., Hagen, L., Krokan, H. E., and Slupphaug, G. (2002) hUNG2 is the Major Repair Enzyme for Removal of Uracil from U:A Matches, U:G Mismatches, and U in Single-Stranded DNA, with hSMUG1 as a Broad Specificity Backup J. Biol. Chem. 277, 39926-39936 (Pubitemid 35190979)
4. Blackburn, G. M. and Walcher, G. (2001) No Strain, No Gain": Studies in the Mechanism of a DNA Repair Enzyme Pol. J. Chem. 75, 1183-1194
5. Stivers, J. T. and Jiang, Y. L. (2003) A Mechanistic Perspective on the Chemistry of DNA Repair Glycosylases Chem. Rev. (Washington, DC, U. S.) 103, 2729-2759
6. Berti, P. J. and McCann, J. A. B. (2006) Toward a Detailed Understanding of Base Excision Repair Enzymes: Transition State and Mechanistic Analyses of N-glycoside Hydrolysis and N-glycoside Transfer Chem. Rev. (Washington, DC, U. S.) 106, 506-555
7. Dong, J., Drohat, A. C., Stivers, J. T., Pankiewicz, K. W., and Carey, P. R. (2000) Raman Spectroscopy of Uracil DNA Glycosylase-DNA Complexes: Insights into DNA Damage Recognition and Catalysis Biochemistry 39, 13241-13250
8. Werner, R. M. and Stivers, J. T. (2000) Kinetic Isotope Effect Studies of the Reaction Catalyzed by Uracil DNA Glycosylase: Evidence for an Oxocarbenium Ion-Uracil Anion Intermediate Biochemistry 39, 14054-14064
9. Mol, C. D., Arvai, A. S., Sanderson, R. J., Slupphaug, G., Kavli, B., Krokan, H. E., Mosbaugh, D. W., and Tainer, J. A. (1995) Crystal Structure of Human Uracil-DNA Glycosylase in Complex with a Protein Inhibitor: Protein Mimicry of DNA Cell (Cambridge, MA, U. S.) 82, 701-708
10. Mol, C. D., Arvai, A. S., Slupphaug, G., Kavli, B., Alseth, I., Krokan, H. E., and Tainer, J. A. (1995) Crystal Structure and Mutational Analysis of Human Uracil-DNA Glycosylase: Structural Basis of Specificity and Catalysis Cell (Cambridge, MA, U. S.) 80, 869-878
11. Slupphaug, G., Mol, C. D., Kavli, B., Arvai, A. S., Krokan, H. E., and Tainer, J. A. (1996) A Nucleotide-Flipping Mechanism from the Structure of Human Uracil-DNA Glycosylase Bound to DNA Nature (London, U. K.) 384, 87-92 (Pubitemid 26374594)
12. Parikh, S. S., Mol, C. D., Slupphaug, G., Bharati, S., Krokan, H. E., and Tainer, J. A. (1998) Base Excision Repair Initiation Revealed by Crystal Structures and Binding Kinetics of Human Uracil-DNA Glycosylase with DNA EMBO J. 17, 5214-5226 (Pubitemid 28408487)
13. Parikh, S. S., Walcher, G., Jones, G. D., Slupphaug, G., Krokan, H. E., Blackburn, G. M., and Tainer, J. A. (2000) Uracil-DNA Glycosylase-DNA Substrate and Product Structures: Conformational Strain Promotes Catalytic Efficiency by Coupled Stereoelectronic Effects Proc. Natl. Acad. Sci. U.S.A. 97, 5083-5088 (Pubitemid 30313675)
14. Bianchet, M. A., Seiple, L. A., Jiang, Y. L., Ichikawa, Y., Amzel, L. M., and Stivers, J. T. (2003) Electrostatic Guidance of Glycosyl Cation Migration Along the Reaction Coordinate of Uracil DNA Glycosylase Biochemistry 42, 12455-12460 (Pubitemid 37337534)
15. Drohat, A. C., Xiao, G. Y., Tordova, M., Jagadeesh, J., Pankiewicz, K. W., Watanabe, K. A., Gilliland, G. L., and Stivers, J. T. (1999) Heteronuclear NMR and Crystallographic Studies of Wild-Type and H187Q Escherichia coli Uracil DNA Glycosylase: Electrophilic Catalysis of Uracil Expulsion by a Neutral Histidine 187 Biochemistry 38, 11876-11886
16. Drohat, A. C. and Stivers, J. T. (2000) Escherichia coli Uracil DNA Glycosylase: NMR Characterization of the Short Hydrogen Bond from His187 to Uracil O2 Biochemistry 39, 11865-11875
17. Drohat, A. C. and Stivers, J. T. (2000) NMR Evidence for an Unusually Low N1 pK(a) for Uracil Bound to Uracil DNA Glycosylase: Implications for Catalysis J. Am. Chem. Soc. 122, 1840-1841 (Pubitemid 30134246)
18. Parker, J. B. and Stivers, J. T. (2008) Uracil DNA Glycosylase: Revisiting Substrate-Assisted Catalysis by DNA Phosphate Anions Biochemistry 47, 8614-8622
19. Drohat, A. C., Jagadeesh, J., Ferguson, E., and Stivers, J. T. (1999) Role of Electrophilic and General Base Catalysis in the Mechanism of Escherichia coli Uracil DNA Glycosylase Biochemistry 38, 11866-11875
20. Jiang, Y. L., Drohat, A. C., Ichikawa, Y., and Stivers, J. T. (2002) Probing the Limits of Electrostatic Catalysis by Uracil DNA Glycosylase Using Transition State Mimicry and Mutagenesis J. Biol. Chem. 277, 15385-15392 (Pubitemid 34967800)
21. Shaw, R. W., Feller, J. A., and Bloom, L. B. (2004) Contribution of a Conserved Phenylalanine Residue to the Activity of Escherichia coli Uracil DNA Glycosylase DNA Repair 3, 1273-1283 (Pubitemid 39164591)
22. Luo, N., Mehler, E., and Osman, R. (1999) Specificity and Catalysis of Uracil DNA Glycosylase. A Molecular Dynamics Study of Reactant and Product Complexes with DNA Biochemistry 38, 9209-9220
23. Dinner, A. R., Blackburn, G. M., and Karplus, M. (2001) Uracil-DNA Glycosylase Acts by Substrate Autocatalysis Nature (London, U. K.) 413, 752-755 (Pubitemid 33009955)
24. Ma, A., Hu, J., Karplus, M., and Dinner, A. R. (2006) Implications of Alternative Substrate Binding Modes for Catalysis by Uracil-DNA Glycosylase: An Apparent Discrepancy Resolved Biochemistry 45, 13687-13696 (Pubitemid 44788739)
25. Millen, A. L., Archibald, L. A. B., Hunter, K. C., and Wetmore, S. D. (2007) A Kinetic and Thermodynamic Study of the Glycosidic Bond Cleavage in Deoxyuridine J. Phys. Chem. B 111, 3800-3812 (Pubitemid 46724010)
26. Jiang, Y. L., Cao, C., Stivers, J. T., Song, F., and Ichikawa, Y. (2004) The Merits of Bipartite Transition-State Mimics for Inhibition of Uracil DNA Glycosylase Bioorg. Chem. 32, 244-262 (Pubitemid 38798267)
27. Wolfenden, R. (2006) Degrees of Difficulty of Water-Consuming Reactions in the Absence of Enzymes Chem. Rev. (Washington, DC, U. S.) 106, 3379-3396 (Pubitemid 44376941)
28. Parker, J. B., Bianchet, M. A., Krosky, D. J., Friedman, J. I., Amzel, L. M., and Stivers, J. T. (2007) Enzymatic Capture of an Extrahelical Thymine in the Search for Uracil in DNA Nature (London, U. K.) 449, 433-438
29. Norman, D. P. G., Chung, S. J., and Verdine, G. L. (2003) Structural and Biochemical Exploration of a Critical Amino Acid in Human 8-oxoguanine Glycosylase Biochemistry 42, 1564-1572 (Pubitemid 36205963)
30. Fromme, J. C. and Verdine, G. L. (2003) DNA Lesion Recognition by the Bacterial Repair Enzyme MutM J. Biol. Chem. 278, 51543-51548 (Pubitemid 38020397)
31. Fromme, J. C. and Verdine, G. L. (2003) Structure of a Trapped Endonuclease III-DNA Covalent Intermediate EMBO J. 22, 3461-3471 (Pubitemid 36834876)
32. Doublie, S., Bandaru, V., Bond, J. P., and Wallace, S. S. (2004) The Crystal Structure of Human Endonuclease VIII-Like 1 (NEIL1) Reveals a Zincless Finger Motif Required for Glycosylase Activity Proc. Natl. Acad. Sci. U.S.A. 101, 10284-10289 (Pubitemid 38924917)
33. Lau, A. Y., Wyatt, M. D., Glassner, B. J., Samson, L. D., and Ellenberger, T. (2000) Molecular Basis for Discriminating Between Normal and Damaged Bases by the Human Alkyladenine Glycosylase, AAG Proc. Natl. Acad. Sci. U.S.A. 97, 13573-13578
34. Fromme, J. C., Banerjee, A., Huang, S. J., and Verdine, G. L. (2004) Structural Basis for Removal of Adenine Mispaired with 8-Oxoguanine by MutY Adenine DNA Glycosylase Nature (London, U. K.) 427, 652-656 (Pubitemid 38248487)
35. Bowman, B. R., Lee, S., Wang, S. Y., and Verdine, G. L. (2010) Structure of Escherichia coli AlkA in Complex with Undamaged DNA J. Biol. Chem. 285, 35783-35791
36. Humbel, S., Sieber, S., and Morokuma, K. (1996) The IMOMO Method: Integration of Different Levels of Molecular Orbital Approximations for Geometry Optimization of Large Systems: Test for n-Butane Conformation and S(N)2 Reaction: RCl+Cl J. Chem. Phys. 105, 1959-1967 (Pubitemid 126612904)
37. Dapprich, S., Komaromi, I., Byun, K. S., Morokuma, K., and Frisch, M. J. (1999) A New ONIOM Implementation in Gaussian98. Part I. The Calculation of Energies, Gradients, Vibrational Frequencies and Electric Field Derivatives THEOCHEM 462, 1-21
38. Lundberg, M., Kawatsu, T., Vreven, T., Frisch, M. J., and Morokuma, K. (2009) Transition States in a Protein Environment- ONIOM QM:MM Modeling of Isopenicillin N Synthesis J. Chem. Theory Comput. 5, 222-234
39. Stewart, J. J. P. (1989) Optimization of Parameters for Semiemperical Methods. 1. Method J. Comput. Chem. 10, 209-220
40. Stewart, J. J. P. (1989) Optimizations of Parameters for Semiemperical Methods. 2. Applications J. Comput. Chem. 10, 221-264
41. Zhao, Y. and Truhlar, D. G. (2004) Hybrid Meta Density Functional Theory Methods for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions: The MPW1B95 and MPWB1K Models and Comparative Assessments for Hydrogen Bonding and Van der Waals Interactions J. Phys. Chem. A 108, 6908-6918
42. Cisneros, G. A. S., Perera, L., Schaaper, R. M., Pedersen, L. C., London, R. E., Pedersen, L. G., and Darden, T. A. (2009) Reaction Mechanism of the AZAμ Subunit of E. coli DNA Polymerase III: Insights into Active Site Metal Coordination and Catalytically Significant Residues J. Am. Chem. Soc. 131, 1550-1556
43. Parks, J. M., Guo, H., Momany, C., Liang, L., Miller, S. M., Summers, A. O., and Smith, J. C. (2009) Mechanism of Hg-C Protonolysis in the Organomercurial Lyase MerB J. Am. Chem. Soc. 131, 13278-13285
44. Tao, P., Gatti, D. L., and Schlegel, H. B. (2009) The Energy Landscape of 3-Deoxy-d-manno-octulosonate 8-Phosphate Synthase Biochemistry 48, 11706-11714
45. Lonsdale, R., Harvey, J. N., and Mulholland, A. J. (2010) Compound I Reactivity Defines Alkene Oxidation Selectivity in Cytochrome P450cam J. Phys. Chem. B 114, 1156-1162
46. Tao, P., Fisher, J. F., Shi, Q., Mobashery, S., and Schlegel, H. B. (2010) Matrix Metalloproteinase 2 (MMP2) Inhibition: DFT and QM/MM Studies of the Deprotonation-Initialized Ring-Opening Reaction of the Sulfoxide Analogue of SB-3CT J. Phys. Chem. B 114, 1030-1037
47. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, Jr., J. A., Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, N. J., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, Ö., Foresman, J. B., Ortiz, J. V., Cioslowski, J., and Fox, D. J. (2009) Gaussian 09, Revision A.1, Gaussian, Inc., Wallingford, CT.
48. Werner, R. M., Jiang, Y. L., Gordley, R. G., Jagadeesh, G. J., Ladner, J. E., Xiao, G. Y., Tordova, M., Gilliland, G. L., and Stivers, J. T. (2000) Stressing-Out DNA? The Contribution of Serine-Phosphodiester Interactions in Catalysis by Uracil DNA Glycosylase Biochemistry 39, 12585-12594
49. Wittwer, C. U. and Krokan, H. (1985) Uracil-DNA Glycosylase in HeLa S3 Cells: Interconvertibility of 50 and 20 kDa Forms and Similarity of the Nuclear and Mitochondrial Form of the Enzyme Biochim. Biophys. Acta, Protein Struct. Mol. Enzymol. 832, 308-318 (Pubitemid 16160739)
50. Slupphaug, G., Eftedal, I., Kavli, B., Bharati, S., Helle, N. M., Haug, T., Levine, D. W., and Krokan, H. E. (1995) Properties of a Recombinant Human Uracil-DNA Glycosylase from the Ung Gene and Evidence That Ung Encodes the Major Uracil-DNA Glycosylase Biochemistry 34, 128-138
51. Richard, J. P. (1995) A Consideration of the Barrier for Carbocation-Nucleophile Combination Reactions Tetrahedron 51, 1535-1573
52. Richard, J. P., Williams, K. B., and Amyes, T. L. (1999) Intrinsic Barriers for the Reactions of an Oxocarbenium Ion in Water J. Am. Chem. Soc. 121, 8403-8404 (Pubitemid 29444486)
53. Di Laudo, M., Whittleton, S. R., and Wetmore, S. D. (2003) Effects of Hydrogen Bonding on the Acidity of Uracil J. Phys. Chem. A 107, 10406-10413
54. Cleland, W. W. and Kreevoy, M. M. (1994) Low-Barrier Hydrogen-Bonds and Enzymatic Catalysis Science (Washington, DC, U. S.) 264, 1887-1890
55. Dalhus, B., Forsbring, M., Helle, I. H., Vik, E. S., Forstram, R. J., Backe, P. H., Alseth, I., and Bjais, M. (2011) Separation-of-Function Mutants Unravel the Dual-Reaction Mode of Human 8-Oxoguanine DNA Glycosylase Structure (Cambridge, MA, U. S.) 19, 117-127