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)
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)
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)
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)
Homolog4
Company's pipeline of compounds includes a series of peptide drugs that target PCNA (Proliferating Cell Nuclear Antigen) and cell stress responses via APIM, a novel PCNA-interacting Stress Switch Peptide Motif identified in human AlkB homolog 2 (AlkB homolog 2 PCNA Interacting Motif). (biotechandmoney.com)
AlkB homolog 5 (ALKBH5) is a demethylase, and its biological function has not been completely explored in HCC. (biomedcentral.com)
However, the potential roles of the demethylases fat-mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5) in HCC have remained unexamined. (biomedcentral.com)
Protein4
Author Manuscript and RNA repair protein AlkB-derived enzyme mixture was first used to remove methylations at the Watson-Crick face. (cdc.gov)
DNA repair proteins that include the bacterial MutL protein and its eukaryotic homologs. (nih.gov)
DNA repair proteins that include the bacterial MutS DNA mismatch-binding protein and its eukaryotic homologs that function in DNA MISMATCH REPAIR and recombination of DNA during MEIOSIS. (bvsalud.org)
Escherichia4
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)
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)
Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage[J]. Nature, 2002, 419(6903): 174-178. (shsmu.edu.cn)
Methylation4
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)
Methylation of mammalian DNA and histone residues are known to regulate transcription, and the discovery of demethylases that remove methylation in DNA and histones provide a basis for the understanding of dynamic regulation of mammalian gene expression. (cmbn.no)
Epigenetics refers to heritable changes in gene expression without changing the nucleotide sequence of the gene, including DNA methylation, histone modifications, and RNA modifications. (beds.ac.uk)
Substrate1
These enzymes use an Fe(II) cofactor and 2-oxoglutarate co-substrate to oxidize organic substrates. (rcsb.org)
Single-stranded3
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)
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)
Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA . (nih.gov)
Alkylation2
Research of the structural function and regulation mechanism of ALKBH3 will help further understand the molecular mechanism in the DNAalkylation 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)
Coli2
for example, in E. coli, the AlkB enzyme is associated with the repair of damaged DNA. (wikipedia.org)
Using an E. coli strain deficient with ALKB, we found that ALKBH6 complements ALKB deficiency and increases resistance after alkylating agent treatment. (frontiersin.org)
Genome2
CMBN shall take on a leading role in elucidating the role of DNA repair and genome maintenance mechanisms in preventing neurological disease and brain ageing. (cmbn.no)
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)
m7G-Seq utilizes chemical reduction and deamination to selectively convert the m7G site into the basic site, and by reverse transcription enzyme to successfully detect the m7G signal within the mRNA (11). (beds.ac.uk)
Nucleotide1
AlkB hydroxylates an alkylated nucleotide base to produce an unstable product that releases an aldehyde to regenerate the unmodified base. (rcsb.org)
Erasers2
This new field of study extends further understanding of epigenetics from the perspective of RNA, where the terminologies are adopted from epigenetics, including writers, readers, and erasers to categorize epitranscriptomic enzymes. (amegroups.org)
Indeed, cells tightly regulate m 6 A modification using specialized enzymes, m 6 A writers and erasers. (molcells.org)
图1 ALKBH3的催化机制和结构Note: A. Repair mechanism of 1mA-ssDNA by ALKBH3. (shsmu.edu.cn)
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)
Human2
In particular, the loss of ALKBH6 in human pancreatic cancer cells increases alkylating agent-induced DNA damage and significantly decreases cell survival. (frontiersin.org)
Aberrant m 6 A modifications by overactivation or suppression of these enzymes lead to human diseases such as cancer, diabetes, and neurological disorders. (molcells.org)
Tissues2
These enzymes are active in many tissues and cell types, whose dyregulations are linked to a variety of disorders and critical diseases, such as cardiovascular disease ( 9 , 10 ). (amegroups.org)
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)
Species1
These epitranscriptomic enzymes mark all kinds of RNA species, including mRNAs and ncRNAs, such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), miRNAs, and lncRNAs ( 11 ). (amegroups.org)
Family1
Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions. (mit.edu)
Mechanisms1
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)
Remove1
It is a reversible chemical mark catalyzed by the enzymes that deposit and remove methyl groups. (molcells.org)
Reverse1
Thermostable group II intron reverse transcriptase (TGIRTTM) enzymes and methods for their use are the subject of patents and patent applications that have been licensed by the University of Texas at Austin and East Tennessee State University to InGex, LLC. (cdc.gov)
The lifecycle of RNA is more dynamic, where they can be modified by a variety of enzymes. (amegroups.org)
Cell1
APIM Therapeutics is a biotech company committed to the development of DNA repair- and cell cycle control-targeting anti-cancer agents. (biotechandmoney.com)
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)
Cells1
Genes down-regulated in comparison of dendritic cells (DC) stimulated with Pam3Csk4 (TLR1/2 agonist) at 16 h versus DC cells stimulated with CpG DNA (TLR9 agonist) at 16 h. (gsea-msigdb.org)
Products1
RNA is not only a mediator of genomic information encoded in DNA to the final products, proteins. (amegroups.org)