Critical role of magnesium ions in DNA polymerase beta's closing and active site assembly

Journal of the American Chemical Society
Linjing YangTamar Schlick

Abstract

To dissect the effects of the nucleotide-binding and catalytic metal ions on DNA polymerase mechanisms for DNA repair and synthesis, aside from the chemical reaction, we investigate their roles in the conformational transitions between closed and open states and assembly/disassembly of the active site of polymerase beta/DNA complexes before and after the chemical reaction of nucleotide incorporation. Using dynamics simulations, we find that closing before chemical reaction requires both divalent metal ions in the active site while opening after the chemical reaction is triggered by release of the catalytic metal ion. The critical closing is stabilized by the interaction of the incoming nucleotide with conserved catalytic residues (Asp190, Asp192, Asp256) and the two functional magnesium ions; without the catalytic ion, other protein residues (Arg180, Arg183, Gly189) coordinate the incomer's triphosphate group through the nucleotide-binding ion. Because we also note microionic heterogeneity near the active site, Mg(2+) and Na(+) ions can diffuse into the active site relatively rapidly, we suggest that the binding of the catalytic ion itself is not a rate-limiting conformational or overall step. However, geometric adjustments ass...Continue Reading

References

Jan 1, 1991·Annual Review of Biochemistry·H Echols, M F Goodman
May 1, 1990·Protein Engineering·M DelarueP Argos
Jan 1, 1980·Annual Review of Biochemistry·J R Knowles
Jul 19, 1983·Biochemistry·F R BryantS J Benkovic
Jan 1, 1994·Annual Review of Biochemistry·C M Joyce, T A Steitz
Jan 1, 1993·Annual Review of Biochemistry·K A Johnson
Feb 25, 1993·Nucleic Acids Research·D K Braithwaite, J Ito
Jan 1, 1997·Annual Review of Biophysics and Biomolecular Structure·T SchlickM Mandziuk
Feb 14, 1998·Nature Structural Biology·T A Kunkel, S H Wilson
Jan 23, 1999·Current Opinion in Structural Biology·S Doublié, T Ellenberger
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Jun 14, 2000·The Journal of Biological Chemistry·W P OsheroffT A Kunkel
Aug 18, 2000·Mutation Research·W A Beard, S H Wilson
Aug 21, 2002·Biochemistry·Alexander K Showalter, Ming-Daw Tsai
Feb 26, 2003·Biopolymers·Jan FloriánArieh Warshel
May 10, 2003·Structure·William A Beard, Samuel H Wilson
Apr 8, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ravi Radhakrishnan, Tamar Schlick

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Citations

Apr 1, 2009·Journal of Molecular Modeling·Thomas E Exner
Mar 1, 2006·Biochemistry·Chithra HariharanLinda J Reha-Krantz
Sep 22, 2005·Journal of the American Chemical Society·Ravi Radhakrishnan, Tamar Schlick
Sep 9, 2010·Journal of the American Chemical Society·Meredith C FoleyTamar Schlick
Nov 8, 2005·Nature Structural & Molecular Biology·Dmitry G VassylyevIrina Artsimovitch
Aug 13, 2010·Metallomics : Integrated Biometal Science·Joseph E Deweese, Neil Osheroff
Nov 18, 2005·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Bongsup P Cho
Jul 26, 2008·Nucleic Acids Research·Joseph E DeweeseNeil Osheroff
Dec 18, 2007·Journal of Bacteriology·Raquel Paes da RochaRodrigo S Galhardo
Jul 16, 2013·Nucleic Acids Research·Anatoly L BuchachenkoNatalia N Breslavskaya
Aug 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ping LinLee G Pedersen
Apr 15, 2014·Journal of Molecular Modeling·Fredrick Robin Devadoss Victor Paul Raj, Thomas E Exner
Mar 6, 2013·Theoretical Chemistry Accounts·Tamar SchlickSamuel H Wilson
Jul 10, 2014·Biomolecules·Pietro Vidossich, Alessandra Magistrato
Nov 12, 2015·British Journal of Cancer·Daniel DibabaKa He
Mar 21, 2012·Geobiology·N G Holm
Apr 2, 2016·Nucleic Acids Research·Taejin KimTamar Schlick
May 11, 2016·Dental Materials : Official Publication of the Academy of Dental Materials·Francesca CecchinatoJulia R Davies
Oct 19, 2006·Journal of Molecular Graphics & Modelling·Thanyada RungrotmongkolSupa Hannongbua
Jan 13, 2017·Journal of Theoretical Biology·Alexander A Tulub, Vassily E Stefanov
Feb 23, 2018·The Analyst·Liu WangJian Wu
Mar 29, 2014·Journal of Biomedical Materials Research. Part a·Rachel W LiDavid R Nisbet
Aug 19, 2005·The EMBO Journal·Alexandra VaismanWei Yang
Dec 25, 2019·Physical Chemistry Chemical Physics : PCCP·Rabindra Nath MannaBiman Jana
Dec 30, 2014·Physiological Reviews·Jeroen H F de BaaijRené J M Bindels

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