Structure of Formamidopyrimidine-DNA Glycosylase Covalently Complexed to DNA*

Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA. The Schiff base intermediate formed during this reaction betweenEscherichia coli Fpg and DNA was trapped by reduction with sodium borohydride, and the structure of the resulting covalently cross-linked complex was determined at a 2.1-Å resolution. Fpg is a bilobal protein with a wide, positively charged DNA-binding groove. It possesses a conserved zinc finger and a helix-two turn-helix motif that participate in DNA binding. The absolutely conserved residues Lys-56, His-70, Asn-168, and Arg-258 form hydrogen bonds to the phosphodiester backbone of DNA, which is sharply kinked at the lesion site. Residues Met-73, Arg-109, and Phe-110 are inserted into the DNA helix, filling the void created by nucleotide eversion. A deep hydrophobic pocket in the active site is positioned to accommodate an everted base. Structural analysis of the Fpg-DNA complex reveals essential features of damage recognition and the catalytic mechanism of Fpg.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-05-31

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M202058200PMID 11912217
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Structural analysis of an Escherichia coli endonuclease VIII covalent reaction intermediate

  2002cited by this paper
• Combining structural and bioinformatics methods for the analysis of functionally important residues in DNA glycosylases.

  2002cited by this paper
• Coupling of substrate recognition and catalysis by a human base-excision DNA repair protein.

  2001cited by this paper
• The COG database: new developments in phylogenetic classification of proteins from complete genomes

  2001cited by this paper
• DNA bending and a flip‐out mechanism for base excision by the helix–hairpin–helix DNA glycosylase, Escherichia coli AlkA

  2000cited by this paper
• Substrate Specificity and Reaction Mechanism of Murine 8-Oxoguanine-DNA Glycosylase*

  2000cited by this paper
• Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA

  2000cited by this paper
• A-form conformational motifs in ligand-bound DNA structures.

  2000cited by this paper
• Involvement of phylogenetically conserved acidic amino acid residues in catalysis by an oxidative DNA damage enzyme formamidopyrimidine glycosylase.

  2000cited by this paper
• Stressing-out DNA? The contribution of serine-phosphodiester interactions in catalysis by uracil DNA glycosylase.

  2000cited by this paper
• Characterization of a cross-linked DNA-Endonuclease VIII repair complex by electrospray ionization mass spectrometry

  2000cited by this paper
• Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8

  2000cited by this paper
• Initiation of base excision repair: glycosylase mechanisms and structures.

  1999cited by this paper
• A structural snapshot of base-pair opening in DNA.

  1999cited by this paper
• Chemistry of Glycosylases and Endonucleases Involved in Base-Excision Repair.

  1998cited by this paper
• Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil‐DNA glycosylase with DNA

  1998cited by this paper
• Role of lysine-57 in the catalytic activities of Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg protein).

  1998cited by this paper
• Oxidative Nucleobase Modifications Leading to Strand Scission.

  1998cited by this paper
• Crystallography & NMR system: A new software suite for macromolecular structure determination.

  1998cited by this paper
• Effect of single mutations on the structural dynamics of a DNA repair enzyme, the Escherichia coli formamidopyrimidine-DNA glycosylase--a fluorescence study using tryptophan residues as reporter groups.

  1998cited by this paper
• Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: mechanisms for nucleotide flipping and base excision.

  1998cited by this paper
• [20] Processing of X-ray diffraction data collected in oscillation mode.

  1997cited by this paper
• Characterization of Escherichia coli Endonuclease VIII*

  1997cited by this paper
• Escherichia coli endonuclease VIII: cloning, sequencing, and overexpression of the nei structural gene and characterization of nei and nei nth mutants

  1997cited by this paper
• Mechanism of action of base release by Escherichia coli Fpg protein: role of lysine 155 in catalysis.

  1997cited by this paper
• Raster3D: photorealistic molecular graphics.

  1997cited by this paper
• An extensively modified version of MolScript that includes greatly enhanced coloring capabilities.

  1997cited by this paper
• Cloning and characterization of a mammalian 8-oxoguanine DNA glycosylase.

  1997cited by this paper
• Processing of X-ray diffraction data collected in oscillation mode.

  1997cited by this paper
• NH2-terminal Proline Acts as a Nucleophile in the Glycosylase/AP-Lyase Reaction Catalyzed by Escherichia coli Formamidopyrimidine-DNA Glycosylase (Fpg) Protein*

  1997cited by this paper
• Methods used in the structure determination of bovine mitochondrial F1 ATPase.

  1996cited by this paper
• Cloning of a yeast 8-oxoguanine DNA glycosylase reveals the existence of a base-excision DNA-repair protein superfamily.

  1996cited by this paper
• A nucleotide-flipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA

  1996cited by this paper
• 3'- and 5'-strand cleavage reactions catalyzed by the Fpg protein from Escherichia coli occur via successive beta- and delta-elimination mechanisms, respectively.

  1996cited by this paper
• The catalytic mechanism of Fpg protein. Evidence for a Schiff base intermediate and amino terminus localization of the catalytic site

  1995cited by this paper
• Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure.

  1995cited by this paper
• Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli.

  1995cited by this paper
• Substrate specificity of Fpg protein. Recognition and cleavage of oxidatively damaged DNA.

  1994cited by this paper
• Expression of chicken linker histones in E. coli: sources of problems and methods for overcoming some of the difficulties.

  1994cited by this paper
• Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G.C-->T.A transversions in simian kidney cells.

  1993cited by this paper
• Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation

  1993cited by this paper
• Fpg protein of Escherichia coli is a zinc finger protein whose cysteine residues have a structural and/or functional role.

  1993cited by this paper
• Function of the zinc finger in Escherichia coli Fpg protein.

  1993cited by this paper
• REPLACE, a suite of computer programs for molecular-replacement calculations

  1993cited by this paper
• Synthesis of 2'-deoxy-7,8-dihydro-8-oxoguanosine and 2'-deoxy-7,8-dihydro-8-oxoadenosine and their incorporation into oligomeric DNA.

  1992cited by this paper
• The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine)

  1992cited by this paper
• A repair system for 8-oxo-7,8-dihydrodeoxyguanine.

  1992cited by this paper
• Free R value: a novel statistical quantity for assessing the accuracy of crystal structures

  1992cited by this paper
• Free R value: a novel statistical quantity for assessing the accuracy of crystal structures.

  1992cited by this paper
• Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG

  1991cited by this paper
• NMR structural studies of the ionizing radiation adduct 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-Oxo-7H-dG(syn).dA(anti) alignment at lesion site.

  1991cited by this paper
• Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons

  1991cited by this paper
• Improved methods for building protein models in electron density maps and the location of errors in these models.

  1991cited by this paper
• A program to produce both detailed and schematic plots of protein structures

  1991cited by this paper
• Site-specific mutagenesis using a gapped duplex vector: a study of translesion synthesis past 8-oxodeoxyguanosine in E. coli.

  1991cited by this paper
• Stereochemical studies of the beta-elimination reactions at aldehydic abasic sites in DNA: endonuclease III from Escherichia coli, sodium hydroxide, and Lys-Trp-Lys.

  1991cited by this paper
• 8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity.

  1991cited by this paper
• Extension of molecular replacement: a new search strategy based on Patterson correlation refinement

  1990cited by this paper
• The locked rotation function.

  1990cited by this paper
• UV Endonuclease V from Bacteriophage T4 Catalyzes DNA Strand Cleavage at Aldehydic Abasic Sites by a Syn β-Elimination Reaction

  1989cited by this paper
• The MIDAS display system

  1988cited by this paper
• The chemical basis of radiation biology

  1987cited by this paper
• Aromatic-aromatic interaction: a mechanism of protein structure stabilization.

  1985cited by this paper
• A NEW FORCE FIELD FOR MOLECULAR MECHANICAL SIMULATION OF NUCLEIC ACIDS AND PROTEINS

  1984cited by this paper

• Catalytic and Structural Insights into Neil3-Dependent Unhooking of Endogenous Abasic DNA Crosslink

  2026cites this paper
• Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System

  2025cites this paper
• Strand-specific quantification of 8-oxo-dG and apurinic sites via Ligation-Dependent Probe Amplification (LPA)

  2025cites this paper
• NEIL3: A unique DNA glycosylase involved in interstrand DNA crosslink repair.

  2024cites this paper
• Sensitive detection of FPG based on 8-oxoG modified chimeric peptide-DNA enzyme for oxidative damage evaluation.

  2024cites this paper
• Structure and in vivo psoralen DNA crosslink repair activity of mycobacterial Nei2

  2024cites this paper
• Single-molecule dynamic structural biology with vertically arranged DNA on a fluorescence microscope

  2024cites this paper
• Probing the Conformational Restraints of DNA Damage Recognition with β-L-Nucleotides

  2024cites this paper
• Bypass of Abasic Site–Peptide Cross-Links by Human Repair and Translesion DNA Polymerases

  2023cites this paper
• Abasic site–peptide cross-links are blocking lesions repaired by AP endonucleases

  2023cites this paper
• Base excision repair of the N-(2-deoxy-d-erythro-pentofuranosyl)-urea lesion by the hNEIL1 glycosylase

  2023cites this paper
• Mycobacterial helicase Lhr abets resistance to DNA crosslinking agents mitomycin C and cisplatin

  2023cites this paper
• Functional roles and cancer variants of the bifunctional glycosylase NEIL2

  2023cites this paper
• Dynamics of 8-Oxoguanine in DNA: Decisive Effects of Base Pairing and Nucleotide Context.

  2023cites this paper
• Aberrant Repair of 8-Oxoguanine in Short DNA Bulges

  2023cites this paper
• A non-canonical nucleotide from viral genomes interferes with the oxidative DNA damage repair system.

  2023cites this paper
• Conformational Dynamics of Biopolymers in the Course of Their Interaction: Multifaceted Approaches to the Analysis by the Stopped-Flow Technique with Fluorescence Detection

  2023cites this paper
• The influence of cdG on 8-oxodG excision by OGG1 and FPG glycosylases.

  2022cites this paper
• Targeting DNA-Protein Crosslinks via Post-Translational Modifications

  2022cites this paper
• The SOS response-associated peptidase (SRAP) domain of YedK catalyzes ring opening of abasic sites and reversal of its DNA–protein cross-link

  2022cites this paper
• Distinct Mechanisms of Target Search by Endonuclease VIII-like DNA Glycosylases

  2022cites this paper
• Model of abasic site DNA cross-link repair; from the architecture of NEIL3 DNA binding domains to the X-structure model

  2022cites this paper
• Abasic site ring opening and DNA-protein crosslink reversal by the SRAP protein YedK

  2022cites this paper
• Noncatalytic Domains in DNA Glycosylases

  2022cites this paper
• The rate of formation and stability of abasic site interstrand crosslinks in the DNA duplex.

  2022cites this paper
• Stalling of Eukaryotic Translesion DNA Polymerases at DNA-Protein Cross-Links

  2022influential citation
• Recognition of a Clickable Abasic Site Analog by DNA Polymerases and DNA Repair Enzymes

  2022cites this paper
• Computational analysis of the binding mode of 8-oxo-guanine to formamidopyrimidine-DNA glycosylase

  2021cites this paper
• Crystal structure and DNA cleavage mechanism of the restriction DNA glycosylase R.CcoLI from Campylobacter coli

  2021cites this paper
• Consequences and repair of radiation-induced DNA damage: fifty years of fun questions and answers

  2021cites this paper
• Recognition of a Tandem Lesion by DNA Glycosylases Explored Combining Molecular Dynamics and Machine Learning

  2021cites this paper
• How Enzymes, Proteins, and Antibodies Recognize Extended DNAs; General Regularities

  2021cites this paper
• Recognition of a tandem lesion by DNA bacterial formamidopyrimidine glycosylases explored combining molecular dynamics and machine learning

  2021influential citation
• Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links

  2021cites this paper
• DNA glycosylases for 8-oxoguanine repair in Staphylococcus aureus.

  2021cites this paper
• The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.

  2020cites this paper
• α-Amidoamids as New Replacements of Antibiotics—Research on the Chosen K12, R2–R4 E. coli Strains

  2020cites this paper
• Inhibitors of DNA Glycosylases as Prospective Drugs

  2020cites this paper
• Conformational changes of DNA repair glycosylase MutM triggered by DNA binding

  2020cites this paper
• Engineering Photodynamic with Radioactive Therapeutic Systems for Sustainable Molecular Polarity: Autopoiesis Systems

  2020cites this paper
• Structural biology of DNA abasic site protection by SRAP proteins.

  2020cites this paper
• Quantification of a Novel DNA-Protein Cross-Link Product Formed by Reacting Apurinic/Apyrimidinic Sites in DNA with Cysteine Residues in Protein by Liquid Chromatography-Tandem Mass Spectrometry Coupled with the Stable Isotope-Dilution Method.

  2019cites this paper
• Conformational Dynamics of Damage Processing by Human DNA Glycosylase NEIL1.

  2019cites this paper
• A cascade amplification platform assisted with DNAzyme for activity analysis, kinetic study and effector screening of Fpg in vitro.

  2019cites this paper
• Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase

  2019cites this paper
• Requirements for DNA bubble structure for efficient cleavage by helix-two-turn-helix DNA glycosylases.

  2019cites this paper
• Comparative Analysis of Nucleotide Fluorescent Analogs for Registration of DNA Conformational Changes Induced by Interaction with Formamidopyrimidine-DNA Glycosylase Fpg

  2019cites this paper
• Critical Sites of DNA Backbone Integrity for Damaged Base Removal by Formamidopyrimidine-DNA Glycosylase.

  2019cites this paper
• Streptomyces IHF uses multiple interfaces to bind DNA.

  2019cites this paper
• Spectroelectrochemical insights into structural and redox properties of immobilized endonuclease III and its catalytically inactive mutant.

  2018cites this paper
• Computational investigation of oxidative damage to guanine: formation, recognition and removal by DNA repair enzymes in humans and bacteria

  2018cites this paper
• Structural Studies of Nucleic Acids

  2018cites this paper
• Initiating base excision repair in chromatin.

  2018cites this paper
• Residue coevolution reveals functionally important intramolecular interactions in formamidopyrimidine-DNA glycosylase.

  2018cites this paper
• Variable termination sites of DNA polymerases encountering a DNA–protein cross-link

  2018cites this paper
• Pulsed Electron–Electron Double Resonance: Nanoscale Distance Measurement in the Biological, Materials and Chemical Sciences

  2018cites this paper
• Etude des ADN glycosylases de la superfamille structurale Fpg/Nei par modélisation moléculaire, de nouvelles cibles thérapeutiques potentielles dans les stratégies anti-cancer

  2017cites this paper
• Mutational and Kinetic Analysis of Lesion Recognition by Escherichia coli Endonuclease VIII

  2017influential citation
• Aberrant base excision repair pathway of oxidatively damaged DNA: Implications for degenerative diseases☆

  2017cites this paper
• Molecular dynamics simulation of the opposite-base preference and interactions in the active site of formamidopyrimidine-DNA glycosylase

  2017cites this paper
• Mechanism of Discrimination of 8-Oxoguanosine versus Guanosine by Escherichia coli Fpg.

  2017cites this paper
• DNA fluorescent labeling with naphtho[1,2,3-cd]indol-6(2H)-one for investigation of protein-DNA interactions.

  2017cites this paper
• Enzymes in the Base Excision Repair Pathway as Targets for Small Molecule Mediated Therapeutics

  2017cites this paper
• The DNA Glycosylases that Recognize and Remove Free Radical-damaged Pyrimidines

  2017cites this paper
• Repair of 8‐oxo‐7,8‐dihydroguanine in prokaryotic and eukaryotic cells: Properties and biological roles of the Fpg and OGG1 DNA N‐glycosylases☆

  2017cites this paper
• Repair of oxidatively induced DNA damage by DNA glycosylases: Mechanisms of action, substrate specificities and excision kinetics.

  2017cites this paper
• Hide and seek: How do DNA glycosylases locate oxidatively damaged DNA bases amidst a sea of undamaged bases?

  2017cites this paper
• EXPLORING THE REGULATION OF SECONDARY METABOLITES IN STREPTOMYCES

  2017cites this paper
• DNA Deformation-Coupled Recognition of 8-Oxoguanine: Conformational Kinetic Gating in Human DNA Glycosylase.

  2017cites this paper
• Gas-Phase Studies of Formamidopyrimidine Glycosylase (Fpg) Substrates.

  2016cites this paper
• Thermodynamic analysis of fast stages of specific lesion recognition by DNA repair enzymes

  2016cites this paper
• Dispensability of the [4Fe‐4S] cluster in novel homologues of adenine glycosylase MutY

  2016cites this paper
• 8-Oxoguanine Affects DNA Backbone Conformation in the EcoRI Recognition Site and Inhibits Its Cleavage by the Enzyme

  2016cites this paper
• The Metagenome of Utricularia gibba's Traps: Into the Microbial Input to a Carnivorous Plant

  2016cites this paper
• Simulations on Formamidopyrimidine-DNA Glycosylase Protein

  2016cites this paper
• Base excision DNA repair in the embryonic development of the sea urchin, Strongylocentrotus intermedius.

  2016cites this paper
• Visualizing the Search for Radiation-damaged DNA Bases in Real Time.

  2016cites this paper
• The Corynebacterium pseudotuberculosis genome contains two formamidopyrimidine-DNA glycosylase enzymes, only one of which recognizes and excises 8-oxoguanine lesion.

  2016cites this paper
• DNA-Protein Cross-Links: Formation, Structural Identities, and Biological Outcomes.

  2015cites this paper
• DNA damage in blood cells exposed to low‐level lasers

  2015cites this paper
• The nucleoid-associated protein HU enhances 8-oxoguanine base excision by the formamidopyrimidine-DNA glycosylase.

  2015cites this paper
• A dynamic checkpoint in oxidative lesion discrimination by formamidopyrimidine–DNA glycosylase

  2015cites this paper
• Reactivity of damaged pyrimidines: formation of a Schiff base intermediate at the glycosidic bond of saturated dihydrouridine.

  2015cites this paper
• Quantum mechanical study of the β- and δ-lyase reactions during the base excision repair process: application to FPG.

  2015cites this paper
• Etude structurale du mécanisme d'échange de chaînes des dimères de la protéine HU d'E. coli

  2015cites this paper
• Insights into the glycosylase search for damage from single-molecule fluorescence microscopy.

  2014cites this paper
• Computational investigation of glycosylase and β-lyase activity facilitated by proline: applications to FPG and comparisons to hOgg1.

  2014cites this paper
• Etude des dommages de l'ADN impliquant des pontages ADN-protéines et ADN-polyamines

  2014cites this paper
• Altered DNA Repair, Antioxidant and Cellular Proliferation Status as Determinants of Susceptibility to Methylmercury Toxicity in Vitro

  2014cites this paper
• Application of repair enzymes to improve the quality of degraded DNA templates for PCR amplification

  2014cites this paper
• Active destabilization of base pairs by a DNA glycosylase wedge initiates damage recognition

  2014cites this paper
• Two glycosylase families diffusively scan DNA using a wedge residue to probe for and identify oxidatively damaged bases

  2014influential citation
• A highly conserved family of domains related to the DNA-glycosylase fold helps predict multiple novel pathways for RNA modifications

  2014cites this paper
• Ribose-protonated DNA base excision repair: a combined theoretical and experimental study.

  2014cites this paper
• Pulsed Electron Double Resonance in Structural Studies of Spin-Labeled Nucleic Acids

  2013cites this paper
• Structural characterization of a mouse ortholog of human NEIL3 with a marked preference for single-stranded DNA.

  2013influential citation
• Excision of 8‐oxoguanine from methylated CpG dinucleotides by human 8‐oxoguanine DNA glycosylase

  2013cites this paper
• From THE DEPARTMENT OF BIOSCIENCES AND NUTRITION Karolinska Institutet, Stockholm, Sweden TOXICITY OF METAL CONTAINING MICRO- AND NANOPARTICLES

  2013cites this paper
• Direct DNA Lesion Reversal and Excision Repair in Escherichia coli

  2013influential citation
• Sculpting of DNA at abasic sites by DNA glycosylase homolog mag2.

  2013cites this paper