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DNA RepairEscherichia coli ProteinsEscherichia coliDNA Repair EnzymesDNA GlycosylasesEscherichia coli InfectionsDNA Polymerase IMolecular Sequence DataDNA, BacterialN-Glycosyl HydrolasesBase SequenceDNA DamageBacterial ProteinsGenes, BacterialAmino Acid SequenceDNA Polymerase IIIMutationPlasmidsDNA-(Apurinic or Apyrimidinic Site) LyaseDeoxyribodipyrimidine Photo-LyaseEscherichia coli O157Uracil-DNA GlycosidaseCloning, MolecularEndodeoxyribonucleasesDNADeoxyribonuclease (Pyrimidine Dimer)Deoxyribonuclease IV (Phage T4-Induced)DNA-Formamidopyrimidine GlycosylaseKineticsUltraviolet RaysDNA ReplicationCarbon-Oxygen LyasesDNA-Directed DNA PolymeraseEscherichia coli K12Substrate SpecificityO(6)-Methylguanine-DNA MethyltransferaseBinding SitesDNA LigasesGuanineDNA-Binding ProteinsDNA, Single-StrandedThymineColiphagesGene Expression Regulation, BacterialSequence Homology, Amino AcidRecombinant ProteinsTemplates, GeneticModels, MolecularExodeoxyribonucleasesAdhesins, Escherichia coliOperonExodeoxyribonuclease VDNA Polymerase betaProtein BindingPyrimidine DimersChromosomes, BacterialGenetic Complementation TestPolynucleotide 5'-Hydroxyl-KinaseDNA, SuperhelicalDNA Topoisomerases, Type IKorarchaeotaEndonucleasesOligodeoxyribonucleotidesGenesDNA HelicasesCatalysisAdenosine TriphosphatasesMutagenesisBacteriophage phi X 174Protein ConformationMethyl MethanesulfonateTranscription, GeneticRestriction MappingMutagenesis, Site-DirectedNucleic Acid ConformationDeoxyguanosineRNA, BacterialAlkylating AgentsSOS Response (Genetics)ExonucleasesDNA PrimersBase Pair MismatchElectrophoresis, Polyacrylamide GelRecombination, GeneticSequence AlignmentCrystallography, X-RayOligonucleotidesUracilTemperaturePoly(ADP-ribose) PolymerasesAlkylationProtein Structure, TertiaryDNA Topoisomerases, Type IIMethyltransferasesDNA Polymerase IIMutagensMolecular WeightDNA Restriction EnzymesBacterial Outer Membrane ProteinsDeoxyribonucleotides
Dioxygenase familyProteinsProteinAlkylationDeficientDemethylationDealkylationSingle-strandedResistanceSubstrateMetabolicDioxygenasesSequenceGeneRoleHumanDamageResponseAgentAlkylationDioxygenaseInhibitionCytochromeHomologsProteinsMethyltransferaseMRNABacterialInhibitorsWeaklyCellsClassStructureCancer
Dioxygenase family3
  • Repair of DNA alkylation damage is essential for maintaining genome integrity and Fe(II)/2-oxoglutarate(2OG)-dependent dioxygenase family of enzymes play crucial role in repairing some of the alkylation damages. (bvsalud.org)
  • Alkylation repair protein-B (AlkB) of Escherichia coli belongs to Fe(II)/2OG-dependent dioxygenase family and carries out DNA dealkylation repair. (bvsalud.org)
  • Human nucleic acid alkylation damage repair enzyme ALKBH3 (alpha-ketoglutarate-dependent dioxygenase homolog 3) belongs to Fe 2+ /α-Ketoglutarate (α-KG)-dependent AlkB dioxygenase family, and shares a highly conserved catalytic domain through the entire family. (shsmu.edu.cn)
Proteins2
  • Escherichia coli AlkB and the homologous human proteins ABH2 and ABH3 (refs 5, 7) promiscuously repair DNA and RNA bases damaged by S(N)2 alkylation reagents, which attach hydrocarbons to endocyclic ring nitrogen atoms (N1 of adenine and guanine and N3 of thymine and cytosine). (rcsb.org)
  • The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. (regenerativemedicine.net)
Protein2
  • In mammals and humans, αKG-dependent dioxygenase have functional roles in biosyntheses (e.g. collagen biosynthesis and L-carnitine biosynthesis), post-translational modifications (e.g. protein hydroxylation), epigenetic regulations (e.g. histone and DNA demethylation), as well as sensors of energy metabolism. (wikipedia.org)
  • ML0190) from the genomic database and show that this 615-bp open reading frame encodes a protein with sequence and structural similarity to Fe(II)/2OG-dependent dioxygenase AlkB. (bvsalud.org)
Alkylation4
  • Heterologous expression of ML0190 in methyl methane sulfonate (MMS) sensitive and DNA repair deficient strain of Saccharomyces cerevisiae and Escherichia coli resulted in resistance to alkylating agent MM. The results of the present study imply that Mycobacterium leprae ML0190 is involved in protecting the bacterial genome from DNA alkylation damage. (bvsalud.org)
  • ALKBH3 specifically recognizes N 1 -methyl adenine and N 3 -methyl cytosine on single-stranded DNA or RNA, and catalyzes their methyl group removal for alkylation damage repair. (shsmu.edu.cn)
  • Research of the structural function and regulation mechanism of ALKBH3 will help further understand the molecular mechanism in the DNA alkylation damage repair, and lay the foundation for the development of anti-tumor drugs targeting ALKBH3. (shsmu.edu.cn)
  • Function of human nucleic acid alkylation damage repair enzyme ALKBH3 in cancer progression and oncotherapy[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(5): 684-689. (shsmu.edu.cn)
Deficient1
  • Using an E. coli strain deficient with ALKB, we found that ALKBH6 complements ALKB deficiency and increases resistance after alkylating agent treatment. (frontiersin.org)
Demethylation1
Dealkylation1
Single-stranded1
  • In comparison, the SN2 agent methyl methane sulfonate (MMS) induces N 1 -methyladenine (m 1 A) and N 3 -methylcytosine (m 3 C) lesions, preferably in single-stranded DNA (ssDNA). (frontiersin.org)
Resistance1
  • The extremely low 5-year overall survival of patients is, in part, due to pancreatic cancer cells having several mechanisms of resistance to different chemotherapeutic treatments, one of which is their capacity to efficiently repair alkylating agent-induced DNA damage. (frontiersin.org)
Substrate3
  • The inhibitors that were regularly used to target αKG-dependent dioxygenase include N-oxalylglycine (NOG), pyridine-2,4-dicarboxylic acid (2,4-PDCA), 5-carboxy-8-hydroxyquinoline, FG-2216 and FG-4592, which were all designed mimic the co-substrate αKG and compete against the binding of αKG at the enzyme active site Fe(II). (wikipedia.org)
  • These enzymes use an Fe(II) cofactor and 2-oxoglutarate co-substrate to oxidize organic substrates. (rcsb.org)
  • Here we have determined crystal structures of substrate and product complexes of E. coli AlkB at resolutions from 1.8 to 2.3 A. Whereas the Fe-2-oxoglutarate dioxygenase core matches that in other superfamily members, a unique subdomain holds a methylated trinucleotide substrate into the active site through contacts to the polynucleotide backbone. (rcsb.org)
Metabolic1
  • In particular, certain types of ALKBH enzymes are dioxygenases that directly reverse DNA methylation damage via transfer of a methyl group from the DNA adduct onto α-ketoglutarate and release of metabolic products including succinate and formaldehyde. (frontiersin.org)
Dioxygenases1
  • Many assays were developed to study αKG-dependent dioxygenases so that information such as enzyme kinetics, enzyme inhibition and ligand binding can be obtained. (wikipedia.org)
Sequence1
  • Although the role of AlkB in DNA repair has long been established based on phenotypic studies, its exact biochemical activity was only elucidated recently after sequence profile analysis revealed it to be a member of the Fe-oxoglutarate-dependent dioxygenase superfamily. (rcsb.org)
Gene1
Role1
  • Here, we tested whether ALKBH6 plays a significant role in preventing alkylating DNA damage and decreasing genomic instability in pancreatic cancer cells. (frontiersin.org)
Human1
  • In particular, the loss of ALKBH6 in human pancreatic cancer cells increases alkylating agent-induced DNA damage and significantly decreases cell survival. (frontiersin.org)
Damage5
  • Importantly, alkylating agents induce DNA damage at different genomic sites, which subsequently leads to lethal and/or mutagenic DNA base lesions. (frontiersin.org)
  • Several alkylating agents are commonly used in chemotherapy but may induce DNA damage to cancer cells as well as normal cells. (frontiersin.org)
  • Sedgwick B. Repairing DNA-methylation damage[J]. Nat Rev Mol Cell Biol, 2004, 5(2): 148-157. (shsmu.edu.cn)
  • Instead, a specific subset of ISGs that includes Parp9 remains activated by the unphosphorylated form of ISGF3 that enhances nDNA damage and repair responses. (regenerativemedicine.net)
  • Therefore, we propose that damage to and subsequent release of mtDNA elicits a protective signalling response that enhances nDNA repair in cells and tissues, suggesting that mtDNA is a genotoxic stress sentinel. (regenerativemedicine.net)
Response1
  • Adaptive response enzyme AlkB preferentially repairs 1-methylguanine and 3-methylthymine adducts in double-stranded DNA[J]. Chem Res Toxicol, 2016, 29(4): 687-693. (shsmu.edu.cn)
Agent1
  • Taverna P, Sedgwick B. Generation of an endogenous DNA-methylating agent by nitrosation in Escherichia coli [J]. J Bacteriol, 1996, 178(17): 5105-5111. (shsmu.edu.cn)
Alkylation12
  • The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond. (nih.gov)
  • The prototypical and homonymous family member is an Escherichia coli 'adaptive response' protein that protects the bacterial genome against alkylation damage. (nih.gov)
  • DNA alkylation damage, emanating from the exposure to environmental alkylating agents or produced by certain endogenous metabolic processes, affects cell viability and genomic stability. (iith.ac.in)
  • Fe(II)/2-oxoglutarate-dependent dioxygenase enzymes, such as Escherichia coli AlkB, are involved in protecting DNA from alkylation damage. (iith.ac.in)
  • We have determined the binding affinity, mode of interaction, and kinetic parameters of inhibition of 3o and tested its ability to sensitize cells to methyl methanesulfonate that mainly produce DNA alkylation damage. (iith.ac.in)
  • Repair of DNA alkylation damage is essential for maintaining genome integrity and Fe(II)/2-oxoglutarate(2OG)-dependent dioxygenase family of enzymes play crucial role in repairing some of the alkylation damages. (bvsalud.org)
  • Alkylation repair protein-B (AlkB) of Escherichia coli belongs to Fe(II)/2OG-dependent dioxygenase family and carries out DNA dealkylation repair. (bvsalud.org)
  • Heterologous expression of ML0190 in methyl methane sulfonate (MMS) sensitive and DNA repair deficient strain of Saccharomyces cerevisiae and Escherichia coli resulted in resistance to alkylating agent MM. The results of the present study imply that Mycobacterium leprae ML0190 is involved in protecting the bacterial genome from DNA alkylation damage. (bvsalud.org)
  • 6. Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes. (nih.gov)
  • 11. The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity. (nih.gov)
  • 13. Oxidative demethylase ALKBH5 repairs DNA alkylation damage and protects against alkylation-induced toxicity. (nih.gov)
  • endobj Another alkylation response protein, the DNA-binding flavoprotein AidB, was proposed to repair DNA or … h�b``�g``^�����)Ā While contractors typically know what they all stand for, clients often do not. (rixt.info)
Dioxygenase6
  • In mammals and humans, αKG-dependent dioxygenase have functional roles in biosyntheses (e.g. collagen biosynthesis and L-carnitine biosynthesis), post-translational modifications (e.g. protein hydroxylation), epigenetic regulations (e.g. histone and DNA demethylation), as well as sensors of energy metabolism. (wikipedia.org)
  • The inhibitors that were regularly used to target αKG-dependent dioxygenase include N-oxalylglycine (NOG), pyridine-2,4-dicarboxylic acid (2,4-PDCA), 5-carboxy-8-hydroxyquinoline, FG-2216 and FG-4592, which were all designed mimic the co-substrate αKG and compete against the binding of αKG at the enzyme active site Fe(II). (wikipedia.org)
  • This study established the potential of indenone-derived compounds as inhibitors of Fe(II)/2-oxoglutarate-dependent dioxygenase AlkB. (iith.ac.in)
  • ML0190) from the genomic database and show that this 615-bp open reading frame encodes a protein with sequence and structural similarity to Fe(II)/2OG-dependent dioxygenase AlkB. (bvsalud.org)
  • 15. Drosophila Alpha-ketoglutarate-dependent dioxygenase AlkB is involved in repair from neuronal disorders induced by ultraviolet damage. (nih.gov)
  • AlkB dioxygenase and Ada methyltransferase in the direct repair of alkylated DNA. (nih.gov)
Inhibition1
  • Many assays were developed to study αKG-dependent dioxygenases so that information such as enzyme kinetics, enzyme inhibition and ligand binding can be obtained. (wikipedia.org)
Cytochrome1
  • Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes. (wikipedia.org)
Homologs3
  • Nine mammalian AlkB homologs exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes. (nih.gov)
  • This minireview presents an overview of the AlkB proteins including recent data on homologs, structural features, substrate specificities, and experimental strategies for studying DNA repair by AlkB family proteins. (nih.gov)
  • 10. Non-homologous functions of the AlkB homologs. (nih.gov)
Proteins1
  • Also, we should shift our attention from DNA to proteins and/or other molecules that offer a much broader and more vulnerable target for metal interactions. (nih.gov)
Methyltransferase1
  • 6-O-methylguanine DNA methyltransferase [Interproscan]. (ntu.edu.sg)
MRNA1
  • 19. AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. (nih.gov)
Bacterial1
Inhibitors1
  • The binding of the ketoglutarate has been observed using enzyme inhibitors. (wikipedia.org)
Weakly1
  • NaDCC was inserted in a plastic garbage can where LB agar plates, with different dilutions of a known title of four different microorganisms (Escherichia coli, Staphylococcus aureus, Debaryomyces hansenii and Aspergillus brasiliensis), were weakly inserted. (bvsalud.org)
Cells2
Class1
  • Inspired by the natural product indenone derivatives reported to inhibit this class of enzymes, and a set of 2-chloro-3-amino indenone derivatives was synthesized and screened for their inhibitory properties against AlkB. (iith.ac.in)
Structure1
  • Structure and mechanism of the alkane-oxidizing enzyme AlkB. (nih.gov)
Cancer1
  • In this study, delivery vehicles comprised of microvesicles loaded with engineered minicircle (MC) DNA that encodes prodrug converting enzymes were developed as a cancer therapy in mammary carcinoma models. (regenerativemedicine.net)