3s9h › Citations

Structural insights into complete metal ion coordination from ternary complexes of B family RB69 DNA polymerase.

Xia S, Wang M, Blaha G, Konigsberg WH, Wang J
Biochemistry 50 9114-24 (2011)
Related entries: 3scx, 3si6, 3sjj, 3snn, 3spy, 3spz, 3sq0, 3sq1

Cited: 29 times
EuropePMC logo PMID: 21923197

Abstract

We have captured a preinsertion ternary complex of RB69 DNA polymerase (RB69pol) containing the 3' hydroxyl group at the terminus of an extendable primer (ptO3') and a nonhydrolyzable 2'-deoxyuridine 5'-α,β-substituted triphosphate, dUpXpp, where X is either NH or CH(2), opposite a complementary templating dA nucleotide residue. Here we report four structures of these complexes formed by three different RB69pol variants with catalytically inert Ca(2+) and four other structures with catalytically competent Mn(2+) or Mg(2+). These structures provide new insights into why the complete divalent metal-ion coordination complexes at the A and B sites are required for nucleotidyl transfer. They show that the metal ion in the A site brings ptO3' close to the α-phosphorus atom (Pα) of the incoming dNTP to enable phosphodiester bond formation through simultaneous coordination of both ptO3' and the nonbridging Sp oxygen of the dNTP's α-phosphate. The coordination bond length of metal ion A as well as its ionic radius determines how close ptO3' can approach Pα. These variables are expected to affect the rate of bond formation. The metal ion in the B site brings the pyrophosphate product close enough to Pα to enable pyrophosphorolysis and assist in the departure of the pyrophosphate. In these dUpXpp-containing complexes, ptO3' occupies the vertex of a distorted metal ion A coordination octahedron. When ptO3' is placed at the vertex of an undistorted, idealized metal ion A octahedron, it is within bond formation distance to Pα. This geometric relationship appears to be conserved among DNA polymerases of known structure.

Articles - 3s9h mentioned but not cited (1)

  1. Structural insights into complete metal ion coordination from ternary complexes of B family RB69 DNA polymerase. Xia S, Wang M, Blaha G, Konigsberg WH, Wang J. Biochemistry 50 9114-9124 (2011)


Reviews citing this publication (6)

  1. Different Divalent Cations Alter the Kinetics and Fidelity of DNA Polymerases. Vashishtha AK, Wang J, Konigsberg WH. J Biol Chem 291 20869-20875 (2016)
  2. Herpesvirus DNA polymerases: Structures, functions and inhibitors. Zarrouk K, Piret J, Boivin G. Virus Res 234 177-192 (2017)
  3. RB69 DNA polymerase structure, kinetics, and fidelity. Xia S, Konigsberg WH. Biochemistry 53 2752-2767 (2014)
  4. Utility of the bacteriophage RB69 polymerase gp43 as a surrogate enzyme for herpesvirus orthologs. Bennett N, Götte M. Viruses 5 54-86 (2013)
  5. Two-Metal-Ion Catalysis: Inhibition of DNA Polymerase Activity by a Third Divalent Metal Ion. Wang J, Konigsberg WH. Front Mol Biosci 9 824794 (2022)
  6. Applications of quantum mechanical/molecular mechanical methods to the chemical insertion step of DNA and RNA polymerization. Perera L, Beard WA, Pedersen LG, Wilson SH. Adv Protein Chem Struct Biol 97 83-113 (2014)

Articles citing this publication (22)

  1. DNA mismatch synthesis complexes provide insights into base selectivity of a B family DNA polymerase. Xia S, Wang J, Konigsberg WH. J Am Chem Soc 135 193-202 (2013)
  2. Molecular recognition of canonical and deaminated bases by P. abyssi family B DNA polymerase. Gouge J, Ralec C, Henneke G, Delarue M. J Mol Biol 423 315-336 (2012)
  3. Structures of intermediates along the catalytic cycle of terminal deoxynucleotidyltransferase: dynamical aspects of the two-metal ion mechanism. Gouge J, Rosario S, Romain F, Beguin P, Delarue M. J Mol Biol 425 4334-4352 (2013)
  4. Fluorescence resonance energy transfer studies of DNA polymerase β: the critical role of fingers domain movements and a novel non-covalent step during nucleotide selection. Towle-Weicksel JB, Dalal S, Sohl CD, Doublié S, Anderson KS, Sweasy JB. J Biol Chem 289 16541-16550 (2014)
  5. Probing minor groove hydrogen bonding interactions between RB69 DNA polymerase and DNA. Xia S, Christian TD, Wang J, Konigsberg WH. Biochemistry 51 4343-4353 (2012)
  6. Kinetics and fidelity of polymerization by DNA polymerase III from Sulfolobus solfataricus. Bauer RJ, Begley MT, Trakselis MA. Biochemistry 51 1996-2007 (2012)
  7. Effect of Different Divalent Cations on the Kinetics and Fidelity of RB69 DNA Polymerase. Vashishtha AK, Konigsberg WH. Biochemistry 55 2661-2670 (2016)
  8. Molecular events during translocation and proofreading extracted from 200 static structures of DNA polymerase. Ren Z. Nucleic Acids Res 44 7457-7474 (2016)
  9. Alteration in the cavity size adjacent to the active site of RB69 DNA polymerase changes its conformational dynamics. Xia S, Wood M, Bradley MJ, De La Cruz EM, Konigsberg WH. Nucleic Acids Res 41 9077-9089 (2013)
  10. Structural basis for differential insertion kinetics of dNMPs opposite a difluorotoluene nucleotide residue. Xia S, Eom SH, Konigsberg WH, Wang J. Biochemistry 51 1476-1485 (2012)
  11. Bidentate and tridentate metal-ion coordination states within ternary complexes of RB69 DNA polymerase. Xia S, Eom SH, Konigsberg WH, Wang J. Protein Sci 21 447-451 (2012)
  12. Calcium-driven DNA synthesis by a high-fidelity DNA polymerase. Ralec C, Henry E, Lemor M, Killelea T, Henneke G. Nucleic Acids Res 45 12425-12440 (2017)
  13. Structural basis for the selective incorporation of an artificial nucleotide opposite a DNA adduct by a DNA polymerase. Betz K, Nilforoushan A, Wyss LA, Diederichs K, Sturla SJ, Marx A. Chem Commun (Camb) 53 12704-12707 (2017)
  14. Structural Insights into Binding of Remdesivir Triphosphate within the Replication-Transcription Complex of SARS-CoV-2. Wang J, Shi Y, Reiss K, Maschietto F, Lolis E, Konigsberg WH, Lisi GP, Batista VS. Biochemistry 61 1966-1973 (2022)
  15. A remote palm domain residue of RB69 DNA polymerase is critical for enzyme activity and influences the conformation of the active site. Jacewicz A, Trzemecka A, Guja KE, Plochocka D, Yakubovskaya E, Bebenek A, Garcia-Diaz M. PLoS One 8 e76700 (2013)
  16. Crystallographic evidence for two-metal-ion catalysis in human pol η. Wang J, Smithline ZB. Protein Sci 28 439-447 (2019)
  17. Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι. Choi JY, Patra A, Yeom M, Lee YS, Zhang Q, Egli M, Guengerich FP. J Biol Chem 291 21063-21073 (2016)
  18. Using a fluorescent cytosine analogue tC(o) to probe the effect of the Y567 to Ala substitution on the preinsertion steps of dNMP incorporation by RB69 DNA polymerase. Xia S, Beckman J, Wang J, Konigsberg WH. Biochemistry 51 4609-4617 (2012)
  19. Manganese-Induced Substrate Promiscuity in the Reaction Catalyzed by Phosphoglutamine Cytidylyltransferase from Campylobacter jejuni. Taylor ZW, Raushel FM. Biochemistry 58 2144-2151 (2019)
  20. The effect of different divalent cations on the kinetics and fidelity of Bacillus stearothermophilus DNA polymerase. Vashishtha AK, Konigsberg WH. AIMS Biophys 5 125-143 (2018)
  21. Human Mitochondrial DNA Polymerase Metal Dependent UV Lesion Bypassing Ability. Park J, Baruch-Torres N, Iwai S, Herrmann GK, Brieba LG, Yin YW. Front Mol Biosci 9 808036 (2022)
  22. Structure of New Binary and Ternary DNA Polymerase Complexes From Bacteriophage RB69. Park J, Youn HS, An JY, Lee Y, Eom SH, Wang J. Front Mol Biosci 8 704813 (2021)


Quick links