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Title: Hydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex

Abstract

Results obtained using 2,4-difluorotoluene nucleobase (dF) as a nonpolar thymine isostere by Kool and colleagues challenged the Watson-Crick dogma that hydrogen bonds between complementary bases are an absolute requirement for accurate DNA replication. Here, we report crystal structure of an RB69 DNA polymerase L561A/S565G/Y567A triple mutant ternary complex with a templating dF opposite dTTP at 1.8 {angstrom}-resolution. In this structure, direct hydrogen bonds were observed between: (i) dF and the incoming dTTP, (ii) dF and residue G568 of the polymerase, and (iii) dF and ordered water molecules surrounding the nascent base pair. Therefore, this structure provides evidence that a templating dF can form novel hydrogen bonds with the incoming dTTP and with the enzyme that differ from those formed with a templating dT.

Authors:
; ;  [1]
  1. Yale
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
FOREIGNNIH
OSTI Identifier:
1023683
Resource Type:
Journal Article
Journal Name:
J. Am. Chem. Soc.
Additional Journal Information:
Journal Volume: 133; Journal Issue: (26) ; 07, 2011; Journal ID: ISSN 0002-7863
Country of Publication:
United States
Language:
ENGLISH
Subject:
08 HYDROGEN; CRYSTAL STRUCTURE; DNA POLYMERASES; DNA REPLICATION; ENZYMES; HYDROGEN; MOLECULES; MUTANTS; NUCLEOTIDES; RESIDUES; THYMINE; WATER

Citation Formats

Xia, Shuangluo, Konigsberg, William H, and Wang, Jimin. Hydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex. United States: N. p., 2011. Web. doi:10.1021/ja2021735.
Xia, Shuangluo, Konigsberg, William H, & Wang, Jimin. Hydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex. United States. https://doi.org/10.1021/ja2021735
Xia, Shuangluo, Konigsberg, William H, and Wang, Jimin. 2011. "Hydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex". United States. https://doi.org/10.1021/ja2021735.
@article{osti_1023683,
title = {Hydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex},
author = {Xia, Shuangluo and Konigsberg, William H and Wang, Jimin},
abstractNote = {Results obtained using 2,4-difluorotoluene nucleobase (dF) as a nonpolar thymine isostere by Kool and colleagues challenged the Watson-Crick dogma that hydrogen bonds between complementary bases are an absolute requirement for accurate DNA replication. Here, we report crystal structure of an RB69 DNA polymerase L561A/S565G/Y567A triple mutant ternary complex with a templating dF opposite dTTP at 1.8 {angstrom}-resolution. In this structure, direct hydrogen bonds were observed between: (i) dF and the incoming dTTP, (ii) dF and residue G568 of the polymerase, and (iii) dF and ordered water molecules surrounding the nascent base pair. Therefore, this structure provides evidence that a templating dF can form novel hydrogen bonds with the incoming dTTP and with the enzyme that differ from those formed with a templating dT.},
doi = {10.1021/ja2021735},
url = {https://www.osti.gov/biblio/1023683}, journal = {J. Am. Chem. Soc.},
issn = {0002-7863},
number = (26) ; 07, 2011,
volume = 133,
place = {United States},
year = {Mon Aug 29 00:00:00 EDT 2011},
month = {Mon Aug 29 00:00:00 EDT 2011}
}