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Literature summary for 1.2.1.12 extracted from

  • Kosova, A.A.; Khodyreva, S.N.; Lavrik, O.I.
    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with apurinic/apyrimidinic sites in DNA (2015), Mutat. Res., 779, 46-57 .
    View publication on PubMed
Search for more literature for 1.2.1.12

Cloned(Commentary)

Cloned (Comment) Organism
DNA and amino acid sequence determination of isozyme uracil-DNA glycosylase, UDG Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
tris(2-carboxyethyl)phosphine a reducing agent to break the disulfide bonds, inhibits formation of the GAPDH-AP DNA-borohydride-independent adduct Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
nucleus isozyme uracil-DNA glycosylase localizes in the nucleus as a monomer, UDG, or a dimer (RNA-binding form), but not in the native tetrameric form Homo sapiens 5634
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
D-glyceraldehyde 3-phosphate + phosphate + NAD+ Homo sapiens
-
 3-phospho-D-glyceroyl phosphate + NADH + H+
-
 ?
D-glyceraldehyde 3-phosphate + phosphate + NAD+ Oryctolagus cuniculus
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 3-phospho-D-glyceroyl phosphate + NADH + H+
-
 ?
additional information Homo sapiens GAPDH interacts with DNA damages, such as uracil ?
-
 ?
additional information Oryctolagus cuniculus GAPDH interacts with DNA damages, such as uracil ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P04406
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-
Oryctolagus cuniculus P46406
-
-

Purification (Commentary)

Purification (Comment) Organism
native enzyme from HeLa cells by ammonium sulfate fractionation followed by the heparin affinity chromatography, anion exchange chromatgraphy, and gel filtration Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
C33A cell
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 Homo sapiens
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cervical adenocarcinoma cell
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 Homo sapiens
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HeLa cell immunodetection of GAPDH and its adducts with apurinic/apyrimidinic DNA in cell extracts Homo sapiens
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SiHa cell
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 Homo sapiens
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skeletal muscle
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 Oryctolagus cuniculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-glyceraldehyde 3-phosphate + phosphate + NAD+
-
 Homo sapiens 3-phospho-D-glyceroyl phosphate + NADH + H+
-
 ?
D-glyceraldehyde 3-phosphate + phosphate + NAD+
-
 Oryctolagus cuniculus 3-phospho-D-glyceroyl phosphate + NADH + H+
-
 ?
additional information GAPDH interacts with DNA damages, such as uracil Homo sapiens ?
-
 ?
additional information GAPDH interacts with DNA damages, such as uracil Oryctolagus cuniculus ?
-
 ?
additional information interaction analysis of the purified enzyme with oligodeoxyribonucleotides, poly(dA-dU) and poly(dA-dT) substrate synthesis, overview. GAPDH, like DNA glycosylases/AP lyases, is able to cleave DNA and to remain bound with the 5'-terminal product of beta-elimination via the Schiff base-dependent bonding. But unlike DNA glycosylases/AP lyases, GAPDH forms considerably more stable complexes with the product of beta-elimination that potentially can make it inefficient as an AP lyase. Lack of the UDG activity in classical GAPDH. Disulfide bond reduction in GAPDH leads to the loss of its ability to form the adducts with AP DNA Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
? x * 35470, apo-form of GADPH isozyme uracil-DNA glycosylase, mass spectrometry Homo sapiens
monomer 1 * 45000, SDS-PAGE, isozyme uracil-DNA glycosylase Oryctolagus cuniculus
monomer 1 * 45000, SDS-PAGE, isozyme uracil-DNA glycosylase, enzyme as adduct with AP DNA Homo sapiens

Synonyms

Synonyms Comment Organism
GAPDH
-
 Homo sapiens
GAPDH
-
 Oryctolagus cuniculus
glyceraldehyde-3-phosphate dehydrogenase
-
 Homo sapiens
glyceraldehyde-3-phosphate dehydrogenase
-
 Oryctolagus cuniculus
UDG
-
 Homo sapiens
uracil-DNA glycosylase
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens
37
-
 assay at Oryctolagus cuniculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Homo sapiens
8
-
 assay at Oryctolagus cuniculus

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Homo sapiens
NAD+
-
 Oryctolagus cuniculus

General Information

General Information Comment Organism
evolution the sequence of the isozyme uracil-DNA glycosylase, UDG polypeptide (331 amino acids), differs from the sequence of classical GAPDH (335 amino acids) by the substitution of the residues 194-213 and the deletion of the residues 328-330. The amino acid sequence of the GAPDH isoform UDG because of its activity is hardly connected with alternative splicing of GAPDH pre-mRNA. The UDG region with the altered amino acids 194-213 is situated within the exon far from its boundaries. It appears to be a result of the single-nucleotide deletion in the GAPDH gene exon, causing the shift of the reading frame. Downstream to this region, there is theadditional deletion of 2 nucleotides in the UDG sequence, leading to restoration of the initial reading frame. The observed discrepancies in the sequences of these proteins are likely due to a sequencing error. Interestingly, the altered region belongs to the GAPDH glyceraldehyde-3-phosphate-binding site not participating in DNA binding Homo sapiens
physiological function apurinic/apyrimidinic (AP) sites are some of the most frequent DNA damages and the key intermediates of base excision repair. Certain proteins can interact with the deoxyribose of the AP site to form a Schiff base, which can be stabilized by NaBH4 treatment. The enzyme interacts with single-stranded AP DNA and AP DNA duplex with both 5' and 3' dangling ends. The protein forming this adduct is an isoform of glyceraldehyde-3-phosphate dehydrogenase called uracil-DNA glycosylase. GAPDH, at least partially, is covalently linked with the AP site by a mechanism other than the Schiff base formation. In spite of the ability to form a Schiff-base intermediate with the deoxyribose of the AP site, GAPDH does not display the AP lyase activity. In addition, along with the borohydride-dependent adducts with AP DNAs containing single-stranded regions, GAPDH was also shown to form the stable borohydride-independent crosslinks with these AP DNAs. GAPDH crosslinks preferentially to AP DNAs cleaves via the beta-elimination mechanism (spontaneously or by AP lyases) as compared to DNAs containing the intact AP site. The level of GAPDH-AP DNA adduct formation depends on oxidation of the protein SH-groups. Disulfide bond reduction in GAPDH leads to the loss of its ability to form the adducts with AP DNA Homo sapiens
physiological function apurinic/apyrimidinic (AP) sites are some of the most frequent DNA damages and the key intermediates of base excision repair. Certain proteins can interact with the deoxyribose of the AP site to form a Schiff base, which can be stabilized by NaBH4 treatment. The enzyme interacts with single-stranded AP DNA and AP DNA duplex with both 5' and 3' dangling ends. The protein forming this adduct is an isoform of glyceraldehyde-3-phosphate dehydrogenase called uracil-DNA glycosylase. GAPDH, at least partially, is covalently linked with the AP site by a mechanism other than the Schiff base formation. In spite of the ability to form a Schiff-base intermediate with the deoxyribose of the AP site, GAPDH does not display the AP lyase activity. In addition, along with the borohydride-dependent adducts with AP DNAs containing single-stranded regions, GAPDH was also shown to form the stable borohydride-independent crosslinks with these AP DNAs. GAPDH crosslinks preferentially to AP DNAs cleaves via the beta-elimination mechanism (spontaneously or by AP lyases) as compared to DNAs containing the intact AP site. The level of GAPDH–AP DNA adduct formation depends on oxidation of the protein SH-groups. Disulfide bond reduction in GAPDH leads to the loss of its ability to form the adducts with AP DNA Oryctolagus cuniculus