Highly organized but pliant active site of DNA polymerase β: Compensatory mechanisms in mutant enzymes revealed by dynamics simulations and energy analyses

Biophysical Journal

Volumn 86, Issue 6, 2004, Pages 3392-3408

  Yang, Linjing ^a   Beard, William A ^b   Wilson, Samuel H ^b   Broyde, Suse ^c   Schlick, Tamar ^a  

^a NEW YORK UNIVERSITY   (United States)

^b NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^c NEW YORK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; ARGININE; ASPARTIC ACID; DNA DIRECTED DNA POLYMERASE BETA; LYSINE; MUTANT PROTEIN; NUCLEOTIDE; VALINE;

ARTICLE; BASE PAIRING; BINDING AFFINITY; CATALYSIS; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; ENERGY; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME KINETICS; ENZYME SPECIFICITY; HUMAN; HYDROGEN BOND; MOLECULAR DYNAMICS; NONHUMAN; PROTEIN DNA INTERACTION; PROTEIN DOMAIN; SIMULATION;

INSERTION SEQUENCES;

EID: 2942666430     PISSN: 00063495     EISSN: None     Source Type: Journal    
DOI: 10.1529/biophysj.103.036012     Document Type: Article

References (73)

1. Ahn, J., V. S. Kraynov, X. Zhong, B. G. Werneburg, and M.-D. Tsai. 1998. DNA polymerase β: effects of gapped DNA substrates on dNTP specificity, fidelity, processivity and conformational changes. Biochem. J. 331:79-87.
2. Ahn, J., B. G. Werneburg, and M.-D. Tsai. 1997. DNA polymerase β: structure-fidelity relationship from pre-steady-state kinetic analyses of all possible correct and incorrect basepairs for wild type and R283A mutant. Biochemistry. 36:1100-1107.
3. Arndt, J. W., W. Gong, X. Zhong, A. K. Showalter, J. Liu, C. A. Dunlap, Z. Lin, C. Paxson, M.-D. Tsai, and M. K. Chan. 2001. Insight into the catalytic mechanism of DNA polymerase β: structures of intermediate complexes. Biochemistry. 40:5368-5375.
4. Arora, K., and T. Schlick. 2003. Deoxyadenosine sugar puckering pathway simulated by the stochastic difference equation algorithm. Chem. Phys. Lett. 378:1-8.
5. Barth, E., and T. Schlick. 1998a. Overcoming stability limitation in biomolecular dynamics. I. Combining force splitting via extrapolation with Langevin dynamics in LN. J. Chem. Phys. 109:1617-1632.
6. Barth, E., and T. Schlick. 1998b. Extrapolation versus impulse in multiple-timestepping schemes. II. Linear analysis and applications to Newtonian and Langevin dynamics. J. Chem. Phys. 109:1633-1642.
7. Beard, W. A., W. P. Osheroff, R. Prasad, M. R. Sawaya, M. Jaju, T. G. Wood, J. Kraut, T. A. Kunkel, and S. H. Wilson. 1996. Enzyme-DNA interactions required for efficient nucleotide incorporation and discrimination in human DNA polymerase β. J. Biol. Chem. 271:12141-12144.
8. Beard, W. A., D. D. Shock, B. J. Vande Berg, and S. H. Wilson. 2002a. Efficiency of correct nucleotide insertion governs DNA polymerase fidelity. J. Biol. Chem. 49:47393-47398.
9. Beard, W. A., D. D. Shock, X.-P. Yang, S. F. DeLauder, and S. H. Wilson. 2002b. Loss of DNA polymerase β stacking interactions with templating purines, but not pyrimidines, alters catalytic efficiency and fidelity. J. Biol. Chem. 277:8235-8242.
10. Beard, W. A., and S. H. Wilson. 1998. Structural insights into DNA polymerase β fidelity: hold tight if you want it right. Chem. Biol. 5:R7-R13.
11. Beard, W. A., and S. H. Wilson. 2000. Structural design of a eukaryotic DNA repair polymerase: DNA polymerase β. Mutat. Res. 460:231-244.
12. Beard, W. A., and S. H. Wilson. 2003. Structural insights into the origins of DNA polymerase fidelity. Structure. 11:489-496.
13. Beese, L. S., V. Derbyshire, and T. A. Steitz. 1993. Structure of DNA polymerase I Klenow fragment bound to duplex DNA. Science. 260:352-355.
14. Berman, H. M., J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne. 2000. The protein data bank. Nucleic Acids Res. 28:235-242.
15. Braithwaite, D. K., and J. Ito. 1993. Compilation, alignment, and phylogenetic relationships of DNA polymerases. Nucleic Acids Res. 21:787-802.
16. Brooks, B. R., R. E. Bruccoleri, B. D. Olafson, D. J. States, S. Swaminathan, and M. Karplus. 1983. CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J. Comp. Chem. 4:187-217.
17. Cann, I. K. O., and Y. Ishino. 1999. Archaeal DNA replication: identifying the pieces to solve a puzzle. Genetics. 152:1249-1267.
18. Chin, K., K. A. Sharp, B. Honig, and A. M. Pyle. 1999. Calculating the electrostatic properties of RNA provides new insights into molecular interactions and function. Nat. Struct. Biol. 6:1055-1061.
19. Dahlberg, M. E., and S. J. Benkovic. 1991. Kinetic mechanism of DNA polymerase I (Klenow fragment): identification of a second conformational change and evaluation of the internal equilibrium constant. Biochemistry. 30:4835-4843.
20. Date, T., S. Yamamoto, K. Tanihara, Y. Nishimoto, and A. Matsukage. 1991. Aspartic acid residues at positions 190 and 192 of rat DNA polymerase β are involved in primer binding. Biochemistry. 30:5286-5292.
21. Delarue, M., O. Poch, N. Tordo, D. Moras, and P. Argos. 1990. An attempt to unify the structure of polymerases. Protein Eng. 3:461-467.
22. Ding, J., K. Das, Y. Hsiou, S. G. Sarafianos, A. D. Clark, Jr., A. Jacobo-Molina, C. Tantillo, S. H. Hughes, and E. Arnold. 1998. Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 Å resolution. J. Mol. Biol. 284:1095-1111.
23. Doublié, S., and T. Ellenberger. 1998. The mechanism of action of T7 DNA polymerase. Curr. Opin. Struct. Biol. 8:704-712.
24. Doublié, S., M. R. Sawaya, and T. Ellenberger. 1999. An open and closed case for all polymerases. Structure. 7:R31-R35.
25. Doublié, S., S. Tabor, A. M. Long, C. C. Richardson, and T. Ellenberger. 1998. Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution. Nature. 391:251-258.
26. Echols, H., and M. F. Goodman, 1991. Fidelity mechanism in DNA replication. Annu. Rev. Biochem. 60:477-511.
27. Frey, M. W., L. C. Sowers, D. P. Millar, and S. J. Benkovic. 1995, The nucleotide analog 2-aminopurine as a spectroscopic probe of nucleotide incorporation by the Klenow fragment of Escherichia coli polymerase I and bacteriophage T4 DNA polymerase. Biochemistry. 34:9185-9192.
28. García-Díaz, M., O. Domínguez, L. A. López-Fernández, L. T. de Lera, M. L. Saníger, J. F. Ruiz, M. Párraga, M. J. García-Ortiz, T. Kirchhoff, J. del Mazo, A. Bemad, and L. Blanco. 2000. DNA polymerase lambda (pol λ), a novel eukaryotic DNA polymerase with a potential role in meiosis. J. Mol. Biol. 301:851-867.
29. Goodman, M. F. 1997. Hydrogen bonding revisited: geometric selection as a principal determinant of DNA replication fidelity. Proc. Natl. Acad. Sci. USA. 94:10493-10495.
30. Huang, H., R. Chopra, G. L. Verdine, and S. C. Harrison. 1998, Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science. 282:1669-1675.
31. Ito, J., and D. K. Braithwaite. 1991. Compilation and alignment of DNA polymerase sequences. Nucleic Acids Res. 19:4045-4057.
32. Iwanaga, A., M. Ouchida, K. Miyazaki, K. Hori, and T. Mukai. 1999. Functional mutation of DNA polymerase β found in human gastric cancer-inability of the base excision repair in vitro. Mutat. Res. 435:121-128.
33. Joyce, C. M., and T. A. Steitz. 1994. Function and structure relationships in DNA polymerases. Annu. Rev. Biochem. 63:777-822.
34. Kati, W. M., K. A. Johnson, L. F. Jerva, and K. S. Anderson. 1992. Mechanism and fidelity of HIV reverse transcriptase. J. Biol. Chem. 267:25988-25997.
35. Kohlstaedt, L. A., J. Wang, J. M. Friedman, P. A. Rice, and T. A. Steitz. 1992. Crystal structures at 3.5 Å of HIV-1 reverse transcriptase complexed with an inhibitor. Science. 256:1783-1790.
36. Kool, E. T., J. C. Morales, and K. M. Guckian. 2000. Mimicking the structure and function of DNA: insight into DNA stability and replication. Angew. Chem. Int. Ed. 39:990-1009.
37. Kraynov, V. S., B. G. Werneburg, X. Zhong, H. Lee, J. Ahn, and M.-D. Tsai. 1997. DNA polymerase β: analysis of the contributions of tyrosine-271 and asparagine-279 to substrate specificity and fidelity of DNA replication by pre-steady-state kinetics. Biochem. J. 323:103-111.
38. Kuchta, R. D., P. Benkovic, and S. J. Benkovic. 1988. Kinetic mechanism whereby DNA polymerase I (Klenow) replicates DNA with high fidelity. Biochemistry. 27:6716-6725.
39. Kunkel, T. A., and K. Bebenek. 2000. DNA replication fidelity. Annu. Rev. Biochem. 69:497-529.
40. Larder, B. A., S. D. Kemp, and D. J. Purifoy. 1989. Infectious potential of human immunodeficiency virus type 1 reverse transcriptase mutants with altered inhibitor sensitivity. Proc. Natl. Acad. Sci. USA. 86:4803-4807.
41. Larder, B. A., D. J. Purifoy, K. L. Powell, and G. Darby. 1987. Site-specific mutagenesis of AIDS virus reverse transcriptase. Nature. 327:716-717.
42. Li, Y., S. Korolev, and G. Waksman. 1998. Crystal structures of open and closed forms of binary and ternary complexes of the large fragment of Thermus aquaticus DNA polymerase I: structural basis for nucleotide incorporation. EMBO J. 17:7514-7525.
43. Ling, H., F. Boudsocq, R. Woodgate, and W. Yang. 2001. Crystal structure of a Y-family DNA polymerase in action: a mechanism for error-prone and lesion-bypass replication. Cell. 107:91-102.
44. Maciejewski, M. W., R. Shin, B. Pan, A. Marintchev, A. Denninger, M. A. Mullen, K. Chen, M. R. Gryk, and G. P. Mullen. 2001. Solution structure of a viral DNA repair polymerase. Nat. Struct. Biol. 8:936-941.
45. MacKerell, A. D., Jr., and N. K. Banavali. 2000. All-atom empirical force field for nucleic acids. II. Application to molecular dynamics simulations of DNA and RNA in solution. J. Comp. Chem. 21:105-120.
46. Menge, K. L., Z. Hostomsky, B. R. Nodes, G. O. Hudson, S. Rahmati, E. W. Moomaw, R. J. Almassy, and Z. Hostomska. 1995. Structure-function analysis of the mammalian DNA polymerase β active site: role of aspartic acid 256, arginine 254 and arginine 258 in nucleotidyl transfer. Biochemistry. 34:15934-15942.
47. Ohmori, H., E. C. Friedberg, R. P. P. Fuchs, M. F. Goodman, F. Hanaoka, D. Hinkle, T. A. Kunkle, C. W. Lawrence, Z. Livneh, T. Nohmi, L. Prakash, S. Prakash, T. Todo, G. C. Walker, Z. Wang, and R. Woodgate. 2001. The Y-family of DNA polymerases. Mol. Cell. 8:7-8.
48. Oliveros, M., R. J. Yúñez, M. L. Salas, J. Salas, E. Viñuela, and L. Blanco. 1997. Characterization of an African swine fever virus 20-kDa DNA polymerase involved in DNA repair. J. Biol. Chem. 272:30899-30910.
49. Ollis, D. L., P. Brick, R. Hamlin, N. G. Xuong, and T. A. Steitz. 1985. Structure of large fragment of Escherichia coli DNA polymerase 1 complexed with dTMP. Nature. 313:762-766.
50. Osheroff, W. P., W. A. Beard, S. H. Wilson, and T. A. Kunkel. 1999. Base substitution specificity of DNA polymerase β depends on interactions in the DNA minor groove. J. Biol. Chem. 274:20749-20752.
51. Patel, S. S., I. Wong, and K. A. Johnson. 1991. Pre-steady-state kinetic analysis of processive DNA replication inducing complete characterization of an exonuclease-deficient mutant. Biochemistry. 30:511-525.
52. Pelletier, H., M. R. Sawaya, A. Kumar, S. H. Wilson, and J. Kraut. 1994. Structures of ternary complexes of rat DNA polymerase β, a DNA template-primer, and ddCTP. Science. 264:1891-1903.
53. Pelletier, H., M. R. Sawaya, W. Wolfle, S. H. Wilson, and J. Kraut. 1996. A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase β. Biochemistry. 35:12762-12777.
54. Polesky, A. H., T. A. Steitz, N. D. Grindley, and C. M. Joyce. 1990. Identification of residues critical for the polymerase activity of the Klenow fragment of DNA polymerase I from Escherichia coli. J. Biol. Chem. 265:14579-14591.
55. Radhakrishnan, R., and T. Schlick. 2003. Orchestration of cooperative events in DNA synthesis and repair mechanism unraveled by transition path sampling of DNA polymerase β's closing. Proc. Natl. Acad. Sci. USA. 101:5970-5975.
56. Reichenberger, S., and P. Pfeiffer. 1998. Cloning, purification and characterization of DNA polymerase β from Xenopus laevis. Eur. J. Biochem. 251:81-90.
57. Sawaya, M. R., H. Pelletier, A. Kumar, S. H. Wilson, and J. Kraut. 1994. Crystal structures of rat DNA polymerase β: evidence for a common polymerase mechanism. Science. 264:1930-1935.
58. Sawaya, M. R., R. Prasad, S. H. Wilson, J. Kraut, and H. Pelletier. 1997. Crystal structures of human DNA polymerase β complexed with gapped and nicked DNA: evidence for an induced fit mechanism. Biochemistry. 36:11205-11215.
59. Schlick, T. 1992. Optimization methods in computational chemistry. In Reviews in Computational Chemistry, Vol. 3. K. B. Lipkowitz, and D. B. Boyd, editors. VCH Publishers, New York, NY. 1-71.
60. Schlick, T. 2001. Time-trimming tricks for dynamic simulations: splitting force updates to reduce computational work. Structure. 9:R45-R53.
61. Schlick, T., E. Barth, and M. Mandziuk. 1997. Biomolecular dynamics at long timesteps: bridging the timescale gap between simulation and experimentation. Annu. Rev. Biophys. Biomol. Struct. 26:181-222.
62. Sharp, K. A., B. Honig, and S. C. Harvey. 1990. Electrical potential of transfer RNAs: codon-anticodon recognition. Biochemistry. 29:340-346.
63. Showalter, A. K., I. L. Byeon, M. Su, and M. Tsai. 2001. Solution structure of a viral DNA polymerase X and evidence for a mutagenic function. Nat. Struct. Biol. 8:942-946.
64. Singh, K., and M. J. Modak. 1998. A unified DNA- and dNTP-binding mode for DNA polymerases. Trends Biochem. Sci. 23:277-281.
65. Steitz, T. A. 1993. DNA- and RNA-dependent DNA polymerases. Curr. Opin. Struct. Biol. 3:31-38.
66. Vande Berg, B. J., W. A. Beard, and S. H. Wilson. 2001. DNA structure and aspartate 276 influence nucleotide binding to human DNA polymerase β. J. Biol. Chem. 276:3408-3416.
67. Wang, J., A. K. M. A. Sattar, C. C. Wang, J. D. Karam, W. H. Konigsberg, and T. A. Steitz. 1997. Crystal structure of a pol α family replication DNA polymerase from bacteriophage RB69. Cell. 89:1087-1099.
68. Werneburg, B. G., J. Ahn, X. Zhong, R. J. Hondal, V. S. Kraynov, and M.-D. Tsai. 1996. DNA polymerase β: pre-steady-state kinetic analysis and roles of arginine-283 in catalysis and fidelity. Biochemistry. 35:7041-7050.
69. Wilson, S. H. 1998. Mammalian base excision repair and DNA polymerase β. Mutat. Res. 407:203-215.
70. Yang, L., W. A. Beard, S. H. Wilson, S. Broyde, and T. Schlick. 2002a. Polymerase β simulations suggest that Arg258 rotation is a slow step rather than large subdomain motion per se. J. Mol. Biol. 317:651-671.
71. Yang, L., W. A. Beard, S. H. Wilson, B. Roux, S. Broyde, and T. Schlick. 2002b. Local deformations revealed by dynamics simulations of DNA polymerase β with DNA mismatches at the primer terminus. J. Mol. Biol. 321:459-478.
72. IIIdTTP. J. Am. Chem. Soc. 120:235-236.
73. Zhong, X., S. S. Patel, B. G. Werneburg, and M.-D. Tsai. 1997. DNA polymerase β: multiple conformational changes in the mechanism of catalysis. Biochemistry. 36:11891-11900.