Aprataxin is a DNA-binding protein that catalyses (among other activities) the 3′ decapping of DNA-ppG (formed by EC 6.5.1.8, 3′-phosphate/5′-hydroxy nucleic acid ligase) . The enzyme binds the guanylate group to a histidine residue at its active site, forming a covalent enzyme-nucleotide phosphate intermediate, followed by the hydrolysis of the guanylate from the nucleic acid and its eventual release. The enzyme also possesses the activity of EC 3.6.1.71, adenosine-5′-diphospho-5′-[DNA] diphosphatase, and EC 3.6.1.70, guanosine-5′-diphospho-5′-[DNA] diphosphatase.
The enzyme appears in viruses and cellular organisms
Aprataxin is a DNA-binding protein that catalyses (among other activities) the 3' decapping of DNA-ppG (formed by EC 6.5.1.8, 3'-phosphate/5'-hydroxy nucleic acid ligase) [1]. The enzyme binds the guanylate group to a histidine residue at its active site, forming a covalent enzyme-nucleotide phosphate intermediate, followed by the hydrolysis of the guanylate from the nucleic acid and its eventual release. The enzyme also possesses the activity of EC 3.6.1.71, adenosine-5'-diphospho-5'-[DNA] diphosphatase, and EC 3.6.1.70, guanosine-5'-diphospho-5'-[DNA] diphosphatase.
Substrates: aprataxin is a DNA 3'-de-capping enzyme, converting DNAppG to DNA3'p and GMP. Aprataxin hydrolyzes inosine and 6-O-methylguanosine caps, but not adeoxyguanosine cap. The enzyme also possesses the activity of EC 3.1.11.7, adenosine-5'-diphospho-5'-[DNA] diphosphatase, and EC 3.1.11.8, guanosine-5'-diphospho-5'-[DNA] diphosphatase Products: -
aprataxin is highly effective as a DNA 3' decapping enzyme, converting DNAppG to DNA3'p and GMP. The biochemical impact of DNA capping is to prevent resection and healing of a 3'-PO4 end, while permitting DNA synthesis, at the price of embedding a ribonucleotide and a diphosphate linkage in the repaired strand
depletion of aprataxin in human SHSY5Y neuroblastoma cells and primary skeletal muscle myoblasts results in mitochondrial dysfunction, revealed by reduced citrate synthase activity and mtDNA copy number. mtDNA, not nuclear DNA, has higher levels of background DNA damage on aprataxin knockdown
APTX suppresses DNA-ligase 11-catalyzed ligation of 8oxoG-containing DNA. In presence of APTX, the catalytic commitment of DNA ligase 1 to erroneous ligation is reduced by 70 and 90%, respectively, for the 8oxoG:A and 8oxoG:C substrates
aprataxin is highly effective as a DNA 3' decapping enzyme, converting DNAppG to DNA3'p and GMP. The biochemical impact of DNA capping is to prevent resection and healing of a 3'-PO4 end, while permitting DNA synthesis, at the price of embedding a ribonucleotide and a diphosphate linkage in the repaired strand
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure in complex with GMP, to 1.5 A resolution. GMP binds at the same position and in the same anti nucleoside conformation as AMP, and aprataxin makes more extensive nucleobase contacts with guanine than with adenine, via a hydrogen bonding network to the guanine O6, N1, N2 base edge
in bone marrow of patients from a phase 2 study of the farnesyltransferase inhibitor tipifarnib in older adults with previously untreated acute myeloid leukemia, te RASGRP1/APTX gene expression ratio predicts response to tipifarnib with the greatest accuracy. RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair
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