1cz0 › Citations

A novel endonuclease mechanism directly visualized for I-PpoI.

Galburt EA, Chevalier B, Tang W, Jurica MS, Flick KE, Monnat RJ, Stoddard BL
Nat Struct Biol 6 1096-9 (1999)
Cited: 68 times
EuropePMC logo PMID: 10581547

Abstract

A novel mechanism of DNA endonucleolytic cleavage has been visualized for the homing endonuclease I-PpoI by trapping the uncleaved enzyme-substrate complex and comparing it to the previously visualized product complex. This enzyme employs a unique single metal mechanism. A magnesium ion is coordinated by an asparagine residue and two DNA oxygen atoms and stabilizes the phosphoanion transition state and the 3'oxygen leaving group. A hydrolytic water molecule is activated by a histidine residue for an in-line attack on the scissile phosphate. A strained enzyme-substrate-metal complex is formed before cleavage, then relaxed during the reaction.

Reviews citing this publication (10)

  1. Structure and function of type II restriction endonucleases. Pingoud A, Jeltsch A. Nucleic Acids Res 29 3705-3727 (2001)
  2. Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Chevalier BS, Stoddard BL. Nucleic Acids Res 29 3757-3774 (2001)
  3. Type II restriction endonucleases--a historical perspective and more. Pingoud A, Wilson GG, Wende W. Nucleic Acids Res 42 7489-7527 (2014)
  4. Structure and function of nucleases in DNA repair: shape, grip and blade of the DNA scissors. Nishino T, Morikawa K. Oncogene 21 9022-9032 (2002)
  5. Homing endonucleases: from basics to therapeutic applications. Marcaida MJ, Muñoz IG, Blanco FJ, Prieto J, Montoya G. Cell Mol Life Sci 67 727-748 (2010)
  6. Roles of metal ions in nucleases. Dupureur CM. Curr Opin Chem Biol 12 250-255 (2008)
  7. Restriction endonucleases: classification, properties, and applications. Williams RJ. Mol Biotechnol 23 225-243 (2003)
  8. One is enough: insights into the two-metal ion nuclease mechanism from global analysis and computational studies. Dupureur CM. Metallomics 2 609-620 (2010)
  9. The use of divalent metal ions by type II topoisomerases. Deweese JE, Osheroff N. Metallomics 2 450-459 (2010)
  10. Structural, functional and evolutionary relationships between homing endonucleases and proteins from their host organisms. Taylor GK, Stoddard BL. Nucleic Acids Res 40 5189-5200 (2012)

Articles citing this publication (58)

  1. Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Drum CL, Yan SZ, Bard J, Shen YQ, Lu D, Soelaiman S, Grabarek Z, Bohm A, Tang WJ. Nature 415 396-402 (2002)
  2. A-form conformational motifs in ligand-bound DNA structures. Lu XJ, Shakked Z, Olson WK. J Mol Biol 300 819-840 (2000)
  3. Design, activity, and structure of a highly specific artificial endonuclease. Chevalier BS, Kortemme T, Chadsey MS, Baker D, Monnat RJ, Stoddard BL. Mol Cell 10 895-905 (2002)
  4. Treble clef finger--a functionally diverse zinc-binding structural motif. Grishin NV. Nucleic Acids Res 29 1703-1714 (2001)
  5. Homing endonucleases from mobile group I introns: discovery to genome engineering. Stoddard BL. Mob DNA 5 7 (2014)
  6. Structural and functional characterization of mitochondrial EndoG, a sugar non-specific nuclease which plays an important role during apoptosis. Schäfer P, Scholz SR, Gimadutdinow O, Cymerman IA, Bujnicki JM, Ruiz-Carrillo A, Pingoud A, Meiss G. J Mol Biol 338 217-228 (2004)
  7. Mechanism and cleavage specificity of the H-N-H endonuclease colicin E9. Pommer AJ, Cal S, Keeble AH, Walker D, Evans SJ, Kühlmann UC, Cooper A, Connolly BA, Hemmings AM, Moore GR, James R, Kleanthous C. J Mol Biol 314 735-749 (2001)
  8. DNA binding and cleavage by the HNH homing endonuclease I-HmuI. Shen BW, Landthaler M, Shub DA, Stoddard BL. J Mol Biol 342 43-56 (2004)
  9. DNA binding and cleavage by the periplasmic nuclease Vvn: a novel structure with a known active site. Li CL, Hor LI, Chang ZF, Tsai LC, Yang WZ, Yuan HS. EMBO J 22 4014-4025 (2003)
  10. Type II restriction endonuclease R.KpnI is a member of the HNH nuclease superfamily. Saravanan M, Bujnicki JM, Cymerman IA, Rao DN, Nagaraja V. Nucleic Acids Res 32 6129-6135 (2004)
  11. Structural insights into the first incision reaction during nucleotide excision repair. Truglio JJ, Rhau B, Croteau DL, Wang L, Skorvaga M, Karakas E, DellaVecchia MJ, Wang H, Van Houten B, Kisker C. EMBO J 24 885-894 (2005)
  12. An equivalent metal ion in one- and two-metal-ion catalysis. Yang W. Nat Struct Mol Biol 15 1228-1231 (2008)
  13. Conserved structural chemistry for incision activity in structurally non-homologous apurinic/apyrimidinic endonuclease APE1 and endonuclease IV DNA repair enzymes. Tsutakawa SE, Shin DS, Mol CD, Izumi T, Arvai AS, Mantha AK, Szczesny B, Ivanov IN, Hosfield DJ, Maiti B, Pique ME, Frankel KA, Hitomi K, Cunningham RP, Mitra S, Tainer JA. J Biol Chem 288 8445-8455 (2013)
  14. DNA binding and degradation by the HNH protein ColE7. Hsia KC, Chak KF, Liang PH, Cheng YS, Ku WY, Yuan HS. Structure 12 205-214 (2004)
  15. The crystal structure of the nuclease domain of colicin E7 suggests a mechanism for binding to double-stranded DNA by the H-N-H endonucleases. Cheng YS, Hsia KC, Doudeva LG, Chak KF, Yuan HS. J Mol Biol 324 227-236 (2002)
  16. Protein-DNA hydrophobic recognition in the minor groove is facilitated by sugar switching. Tolstorukov MY, Jernigan RL, Zhurkin VB. J Mol Biol 337 65-76 (2004)
  17. Mutagenic scan of the H-N-H motif of colicin E9: implications for the mechanistic enzymology of colicins, homing enzymes and apoptotic endonucleases. Walker DC, Georgiou T, Pommer AJ, Walker D, Moore GR, Kleanthous C, James R. Nucleic Acids Res 30 3225-3234 (2002)
  18. Crystal structure of the beta beta alpha-Me type II restriction endonuclease Hpy99I with target DNA. Sokolowska M, Czapinska H, Bochtler M. Nucleic Acids Res 37 3799-3810 (2009)
  19. The zinc ion in the HNH motif of the endonuclease domain of colicin E7 is not required for DNA binding but is essential for DNA hydrolysis. Ku WY, Liu YW, Hsu YC, Liao CC, Liang PH, Yuan HS, Chak KF. Nucleic Acids Res 30 1670-1678 (2002)
  20. Human topoisomerase IIalpha uses a two-metal-ion mechanism for DNA cleavage. Deweese JE, Burgin AB, Osheroff N. Nucleic Acids Res 36 4883-4893 (2008)
  21. Sp1 facilitates DNA double-strand break repair through a nontranscriptional mechanism. Beishline K, Kelly CM, Olofsson BA, Koduri S, Emrich J, Greenberg RA, Azizkhan-Clifford J. Mol Cell Biol 32 3790-3799 (2012)
  22. Metal ions and phosphate binding in the H-N-H motif: crystal structures of the nuclease domain of ColE7/Im7 in complex with a phosphate ion and different divalent metal ions. Sui MJ, Tsai LC, Hsia KC, Doudeva LG, Ku WY, Han GW, Yuan HS. Protein Sci 11 2947-2957 (2002)
  23. Crystal structural analysis and metal-dependent stability and activity studies of the ColE7 endonuclease domain in complex with DNA/Zn2+ or inhibitor/Ni2+. Doudeva LG, Huang H, Hsia KC, Shi Z, Li CL, Shen Y, Cheng YS, Yuan HS. Protein Sci 15 269-280 (2006)
  24. Zinc binding catalytic domain of human tankyrase 1. Lehtiö L, Collins R, van den Berg S, Johansson A, Dahlgren LG, Hammarström M, Helleday T, Holmberg-Schiavone L, Karlberg T, Weigelt J. J Mol Biol 379 136-145 (2008)
  25. Hpy188I-DNA pre- and post-cleavage complexes--snapshots of the GIY-YIG nuclease mediated catalysis. Sokolowska M, Czapinska H, Bochtler M. Nucleic Acids Res 39 1554-1564 (2011)
  26. Identification of a new subfamily of HNH nucleases and experimental characterization of a representative member, HphI restriction endonuclease. Cymerman IA, Obarska A, Skowronek KJ, Lubys A, Bujnicki JM. Proteins 65 867-876 (2006)
  27. Structural characterization of H-1 parvovirus: comparison of infectious virions to empty capsids. Halder S, Nam HJ, Govindasamy L, Vogel M, Dinsart C, Salomé N, McKenna R, Agbandje-McKenna M. J Virol 87 5128-5140 (2013)
  28. The protein gp74 from the bacteriophage HK97 functions as a HNH endonuclease. Moodley S, Maxwell KL, Kanelis V. Protein Sci 21 809-818 (2012)
  29. Biochemical characterization of I-CmoeI reveals that this H-N-H homing endonuclease shares functional similarities with H-N-H colicins. Drouin M, Lucas P, Otis C, Lemieux C, Turmel M. Nucleic Acids Res 28 4566-4572 (2000)
  30. R.KpnI, an HNH superfamily REase, exhibits differential discrimination at non-canonical sequences in the presence of Ca2+ and Mg2+. Saravanan M, Vasu K, Kanakaraj R, Rao DN, Nagaraja V. Nucleic Acids Res 35 2777-2786 (2007)
  31. Functional characterization of isoschizomeric His-Cys box homing endonucleases from Naegleria. Elde M, Willassen NP, Johansen S. Eur J Biochem 267 7257-7266 (2000)
  32. Tetrameric restriction enzymes: expansion to the GIY-YIG nuclease family. Gasiunas G, Sasnauskas G, Tamulaitis G, Urbanke C, Razaniene D, Siksnys V. Nucleic Acids Res 36 938-949 (2008)
  33. Cofactor requirement of HpyAV restriction endonuclease. Chan SH, Opitz L, Higgins L, O'loane D, Xu SY. PLoS One 5 e9071 (2010)
  34. Identification of functionally relevant histidine residues in the apoptotic nuclease CAD. Meiss G, Scholz SR, Korn C, Gimadutdinow O, Pingoud A. Nucleic Acids Res 29 3901-3909 (2001)
  35. Conformational changes and cleavage by the homing endonuclease I-PpoI: a critical role for a leucine residue in the active site. Galburt EA, Chadsey MS, Jurica MS, Chevalier BS, Erho D, Tang W, Monnat RJ, Stoddard BL. J Mol Biol 300 877-887 (2000)
  36. Identification of a single HNH active site in type IIS restriction endonuclease Eco31I. Jakubauskas A, Giedriene J, Bujnicki JM, Janulaitis A. J Mol Biol 370 157-169 (2007)
  37. Altered target site specificity variants of the I-PpoI His-Cys box homing endonuclease. Eklund JL, Ulge UY, Eastberg J, Monnat RJ. Nucleic Acids Res 35 5839-5850 (2007)
  38. Strand-specific contacts and divalent metal ion regulate double-strand break formation by the GIY-YIG homing endonuclease I-BmoI. Carter JM, Friedrich NC, Kleinstiver B, Edgell DR. J Mol Biol 374 306-321 (2007)
  39. Crystal structure of the modification-dependent SRA-HNH endonuclease TagI. Kisiala M, Copelas A, Czapinska H, Xu SY, Bochtler M. Nucleic Acids Res 46 10489-10503 (2018)
  40. Genetic organization and molecular analysis of the EcoVIII restriction-modification system of Escherichia coli E1585-68 and its comparison with isospecific homologs. Mruk I, Kaczorowski T. Appl Environ Microbiol 69 2638-2650 (2003)
  41. Mechanistic insights from the structures of HincII bound to cognate DNA cleaved from addition of Mg2+ and Mn2+. Etzkorn C, Horton NC. J Mol Biol 343 833-849 (2004)
  42. Mutagenesis identifies the critical amino acid residues of human endonuclease G involved in catalysis, magnesium coordination, and substrate specificity. Wu SL, Li CC, Chen JC, Chen YJ, Lin CT, Ho TY, Hsiang CY. J Biomed Sci 16 6 (2009)
  43. Crystal structure of endonuclease G in complex with DNA reveals how it nonspecifically degrades DNA as a homodimer. Lin JL, Wu CC, Yang WZ, Yuan HS. Nucleic Acids Res 44 10480-10490 (2016)
  44. DNA intercalation without flipping in the specific ThaI-DNA complex. Firczuk M, Wojciechowski M, Czapinska H, Bochtler M. Nucleic Acids Res 39 744-754 (2011)
  45. DNA nanomechanics: how proteins deform the double helix. Becker NB, Everaers R. J Chem Phys 130 135102 (2009)
  46. Increasing cleavage specificity and activity of restriction endonuclease KpnI. Vasu K, Nagamalleswari E, Zahran M, Imhof P, Xu SY, Zhu Z, Chan SH, Nagaraja V. Nucleic Acids Res 41 9812-9824 (2013)
  47. Mycobacterium tuberculosis RecA intein possesses a novel ATP-dependent site-specific double-stranded DNA endonuclease activity. Guhan N, Muniyappa K. J Biol Chem 277 16257-16264 (2002)
  48. Structural insights into apoptotic DNA degradation by CED-3 protease suppressor-6 (CPS-6) from Caenorhabditis elegans. Lin JL, Nakagawa A, Lin CL, Hsiao YY, Yang WZ, Wang YT, Doudeva LG, Skeen-Gaar RR, Xue D, Yuan HS. J Biol Chem 287 7110-7120 (2012)
  49. Comprehensive homing endonuclease target site specificity profiling reveals evolutionary constraints and enables genome engineering applications. Li H, Ulge UY, Hovde BT, Doyle LA, Monnat RJ. Nucleic Acids Res 40 2587-2598 (2012)
  50. Identification of a conserved DNA sulfur recognition domain by characterizing the phosphorothioate-specific endonuclease SprMcrA from Streptomyces pristinaespiralis. Yu H, Liu G, Zhao G, Hu W, Wu G, Deng Z, He X. Mol Microbiol 110 484-497 (2018)
  51. Structural characterization of the late competence protein ComFB from Bacillus subtilis. Sysoeva TA, Bane LB, Xiao DY, Bose B, Chilton SS, Gaudet R, Burton BM. Biosci Rep 35 e00183 (2015)
  52. Divalent metal ion differentially regulates the sequential nicking reactions of the GIY-YIG homing endonuclease I-BmoI. Kleinstiver BP, Bérubé-Janzen W, Fernandes AD, Edgell DR. PLoS One 6 e23804 (2011)
  53. Engineering nicking enzymes that preferentially nick 5-methylcytosine-modified DNA. Gutjahr A, Xu SY. Nucleic Acids Res 42 e77 (2014)
  54. Mechanistic insight into the catalytic activity of ββα-metallonucleases from computer simulations: Vibrio vulnificus periplasmic nuclease as a test case. Bueren-Calabuig JA, Coderch C, Rico E, Jiménez-Ruiz A, Gago F. Chembiochem 12 2615-2622 (2011)
  55. Reactions of phosphate and phosphorothiolate diesters with nucleophiles: comparison of transition state structures. Ye JD, Barth CD, Anjaneyulu PS, Tuschl T, Piccirilli JA. Org Biomol Chem 5 2491-2497 (2007)
  56. Amino acid residues in the GIY-YIG endonuclease II of phage T4 affecting sequence recognition and binding as well as catalysis. Lagerbäck P, Carlson K. J Bacteriol 190 5533-5544 (2008)
  57. Role of AP-endonuclease (Ape1) active site residues in stabilization of the reactant enzyme-DNA complex. Batebi H, Dragelj J, Imhof P. Proteins 86 439-453 (2018)
  58. Biochemical and mutagenic analysis of I-CreII reveals distinct but important roles for both the H-N-H and GIY-YIG motifs. Corina LE, Qiu W, Desai A, Herrin DL. Nucleic Acids Res 37 5810-5821 (2009)


Quick links