Abstract
The number of metal ions required for phosphoryl transfer in restriction endonucleases is still an unresolved question in molecular biology. The two Ca2+ and Mn2+ ions observed in the pre- and post-reactive complexes of BamHI conform to the classical two-metal ion choreography. We probed the Mg2+ cofactor positions at the active site of BamHI by molecular dynamics simulations with one and two metal ions present and identified several catalytically relevant sites. These can mark the pathway of a single ion during catalysis, suggesting its critical role, while a regulatory function is proposed for a possible second ion.
References
Ban, C. and Yang, W. (1998). Structural basis for MutH activation in E. coli mismatch repair and relationship of MutH to restriction endonucleases. EMBO J.17, 1526–1534.Search in Google Scholar
Beese, L.S., Friedman, J.M., and Steitz, T.A. (1993). Crystal structures of the Klenow fragment of DNA polymerase I complexed with deoxynucleoside triphosphate and pyrophosphate. Biochemistry32, 14095–14101.10.1021/bi00214a004Search in Google Scholar PubMed
Bickle, T.A. and Krüger, D.H. (1993). Biology of DNA restriction. Microbiol. Rev.57, 434–450.10.1128/mr.57.2.434-450.1993Search in Google Scholar PubMed PubMed Central
Bunting, K.A., Roe, S.M., Headley, A., Brown, T., Savva, R., and Pearl, L.H. (2003). Crystal structure of the Escherichia coli dcm very-short-patch DNA repair endonuclease bound to its reaction product-site in a DNA superhelix. Nucleic Acids Res.31, 1633–1639.10.1093/nar/gkg273Search in Google Scholar PubMed PubMed Central
Chevalier, B.S. and Stoddard, B.L. (2001). Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Nucleic Acids Res.29, 3757–3774.10.1093/nar/29.18.3757Search in Google Scholar PubMed PubMed Central
Cornell, W.D., Cieplak, R., Bayly, C.L., Gould, I.R., Merz, K.M., Ferguson, D.M., Spellmeyer, D.G., Fox, T., Caldwell, J.W., and Kollman, P.A. (1995). A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc.117, 5179–5197.10.1021/ja00124a002Search in Google Scholar
Deibert, G., Grazulis, S., Sasnauskas, G., Siksnys, V., and Huber, R. (2000). Structure of tetrameric restriction endonuclease NgoMIV in complex with cleaved DNA. Nat. Struct. Biol.7, 792–799.10.1038/79032Search in Google Scholar PubMed
Etzkorn, C. and Horton, N.C. (2004a). Ca2+ binding in the active site of HincII: implications for the catalytic mechanism. Biochemistry43, 13256–13270.10.1021/bi0490082Search in Google Scholar PubMed
Etzkorn, C. and Horton, N.C. (2004b). Mechanistic insights from the structures of HincII bound to cognate DNA cleaved from addition of Mg2+ and Mn2+. J. Mol. Biol.343, 833–849.10.1016/j.jmb.2004.08.082Search in Google Scholar PubMed
Florian, J., Goodman, M.F., and Warshel, A. (2003). Computer simulation of the chemical catalysis of DNA polymerases: discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymerase. J. Am. Chem. Soc.125, 8163–8177.10.1021/ja028997oSearch in Google Scholar PubMed
Fothergill, M., Goodman, M.F., Petruska, J., and Warshel, A. (1995). Structure-energy analysis of the role of metal ions in phosphodiester bond hydrolysis by DNA polymerase I. J. Am. Chem. Soc.117, 11619–11627.10.1021/ja00152a001Search in Google Scholar
Fuxreiter, M. and Osman, R. (2001). Probing the general base catalysis in the first step of BamHI action by computer simulations. Biochemistry40, 15017–15023.10.1021/bi010987xSearch in Google Scholar
Glusker, J.P. (1991). Structural aspects of metal liganding to functional groups in proteins. Adv. Protein Chem.42, 1–76.10.1016/S0065-3233(08)60534-3Search in Google Scholar
Hadden, J.M., Declais, A.C., Phillips, S.E., and Lilley, D.M. (2002). Metal ions bound at the active site of the junction-resolving enzyme T7 endonuclease I. EMBO J.21, 3505–3515.10.1093/emboj/cdf337Search in Google Scholar
Hickman, A.B., Li, Y., Mathew, S.V., May, E.W., Craig, N.L., and Dyda, F. (2000). Unexpected structural diversity in DNA recombination: the restriction endonuclease connection. Mol. Cell5, 1025–1034.10.1016/S1097-2765(00)80267-1Search in Google Scholar
Horton, J.R. and Cheng, X. (2000). PvuII endonuclease contains two calcium ions in active sites. J. Mol. Biol.300, 1049–1056.10.1006/jmbi.2000.3938Search in Google Scholar
Horton, N.C. and Perona, J.J. (2004). DNA cleavage by EcoRV endonuclease: two metal ions in three metal ion binding sites. Biochemistry43, 6841–6857.10.1021/bi0499056Search in Google Scholar
Horton, N.C., Newberry, K.J., and Perona, J.J. (1998). Metal ion-mediated substrate-assisted catalysis in type II restriction endonucleases. Proc. Natl. Acad. Sci. USA95, 13489–13494.10.1073/pnas.95.23.13489Search in Google Scholar
Horton, N.C., Connolly, B.A., and Perona, J.J. (2000). Inhibition of EcoRV endonuclease by deoxyribo-3′-S-phophorothiolates: a high resolution X-ray crystallographic study. J. Am. Chem. Soc.122, 3314–3324.10.1021/ja993719jSearch in Google Scholar
Jeltsch, A., Alves, J., Wolfes, H., Maass, G., and Pingoud, A. (1993). Substrate-assisted catalysis in the cleavage of DNA by the EcoRI and EcoRV restriction enzymes. Proc. Natl. Acad. Sci. USA90, 8499–8503.10.1073/pnas.90.18.8499Search in Google Scholar
Jeltsch, A., Pleckaityte, M., Selent, U., Wolfes, H., Siksnys, V., and Pingoud, A. (1995). Evidence for substrate-assisted catalysis in the DNA cleavage of several restriction endonucleases. Gene157, 157–162.10.1016/0378-1119(94)00617-2Search in Google Scholar
Jorgensen, W.L., Chandrashekar, J., Madura, J.D., Impey, R., and Klein, M.L. (1983). Comparison of simple potential functions for simulating liquid water. J. Chem. Phys.79, 926–935.10.1063/1.445869Search in Google Scholar
Kovall, R.A. and Matthews, B.W. (1998). Structural, functional, and evolutionary relationships between λ-exonuclease and the type II restriction endonucleases. Proc. Natl. Acad. Sci. USA95, 7893–7897.10.1073/pnas.95.14.7893Search in Google Scholar
Lee, J.Y., Chang, J., Joseph, N., Ghirlando, R., Rao, D.N., and Yang, W. (2005). MutH complexed with hemi- and unmethylated DNAs: coupling base recognition and DNA cleavage. Mol. Cell20, 155–166.10.1016/j.molcel.2005.08.019Search in Google Scholar
Lovell, S., Goryshin, I.Y., Reznikoff, W.R., and Rayment, I. (2002). Two-metal active site binding of a Tn5 transposase synaptic complex. Nat. Struct. Biol.9, 278–281.10.1038/nsb778Search in Google Scholar
Lukacs, C.M., Kucera, R., Schildkraut, I., and Aggarwal, A.K. (2000). Understanding the immutability of restriction enzymes: crystal structure of BglII and its DNA substrate at 1.5Å resolution. Nat. Struct. Biol.7, 134–140.Search in Google Scholar
Marelius, J., Kolmodin, K., Feierberg, I., and Åqvist, J. (1998). Q: a molecular dynamics program for free energy calculations and empirical valence bond simulations in biomolecular systems. J. Mol. Graph. Model.16, 213–225, 261.10.1016/S1093-3263(98)80006-5Search in Google Scholar
Newman, M., Lunnen, K., Wilson, G., Greci, J., Schildkraut, I., and Phillips, S.E. (1998). Crystal structure of restriction endonuclease BglI bound to its interrupted DNA recognition sequence. EMBO J.17, 5466–5476.10.1093/emboj/17.18.5466Search in Google Scholar
Noble, C.G. and Maxwell, A. (2002). The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism. J. Mol. Biol.318, 361–371.10.1016/S0022-2836(02)00049-9Search in Google Scholar
Nowotny, M. and Yang, W. (2006). Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release. EMBO J.25, 1924–1933.10.1038/sj.emboj.7601076Search in Google Scholar
Pingoud, A., Fuxreiter, M., Pingoud, V., and Wende, W. (2005). Type II restriction endonucleases: structure and mechanism. Cell. Mol. Life Sci.62, 685–707.10.1007/s00018-004-4513-1Search in Google Scholar
Roberts, R.J. and Halford, S.E. (1993). Type II restriction endonucleases. In: Nucleases, S.M. Linn, R.S. Lloyd and R.J. Roberts, eds. (Cold Spring Harbor, NY, USA: Cold Spring Harbor Laboratory Press), pp. 35–88.Search in Google Scholar
Rosenberg, J.M. (1991). Structure and function of restriction endonucleases. Curr. Opin. Struct. Biol.1, 104–113.10.1016/0959-440X(91)90018-OSearch in Google Scholar
Steitz, T.A. and Steitz, J.A. (1993). A general two-metal-ion mechanism for catalytic RNA. Proc. Natl. Acad. Sci. USA90, 6498–6502.10.1073/pnas.90.14.6498Search in Google Scholar
Sträter, N., Lipscomb, W.N., Klabunde, T., and Krebs, B. (1996). Two-metal ion catalysis in enzymatic acyl- and phosphoryl-transfer reactions. Angew. Chem. Int. Ed. Engl.35, 2024–2055.10.1002/anie.199620241Search in Google Scholar
Tsutakawa, S.E., Muto, T., Kawate, T., Jingami, H., Kunishima, N., Ariyoshi, M., Kohda, D., Nakagawa, M., and Morikawa, K. (1999). Crystallographic and functional studies of very short patch repair endonuclease. Mol. Cell3, 621–628.10.1016/S1097-2765(00)80355-XSearch in Google Scholar
Viadiu, H. (1999). Structural study of specificity and catalysis by restriction endonuclease BamHI. Ph.D. thesis, Columbia University, New York, USA.Search in Google Scholar
Viadiu, H. and Aggarwal, A.K. (1998). The role of metals in catalysis by the restriction endonuclease BamHI. Nat. Struct. Biol.5, 910–916.10.1038/2352Search in Google Scholar
Xu, S.Y. and Schildkraut, I. (1991). Isolation of BamHI variants with reduced cleavage activities. J. Biol. Chem.266, 4425–4429.10.1016/S0021-9258(20)64339-3Search in Google Scholar
Yang, W., Lee, J.Y., and Nowotny, M. (2006). Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity. Mol. Cell22, 5–13.10.1016/j.molcel.2006.03.013Search in Google Scholar PubMed
©2007 by Walter de Gruyter Berlin New York