Literature summary for 3.6.1.71 extracted from
Hanaoka, K.; Tanaka, W.; Kayanuma, M.; Shoji, M.
A QM/MM study of the 5'-AMP DNA hydrolysis of aprataxin (2015), Chem. Phys. Lett., 631-632, 16-20 .
No PubMed abstract available
Protein Variants
Protein Variants |
Comment |
Organism |
H138A |
site-directed mutagenesis, mutation of His138 to alanine does not completely abolish the catalytic activity, the residual activity is 25% of the wild-type enzyme activity. The DNA deadenylation reaction catalyzed by the H138A mutant can proceed by the protonated substrate |
Homo sapiens |
Natural Substrates/ Products (Substrates)
Natural Substrates |
Organism |
Comment (Nat. Sub.) |
Natural Products |
Comment (Nat. Pro.) |
Rev. |
Reac. |
additional information |
Homo sapiens |
aprataxin hydrolyses abnormal 5'-AMP DNA termini formed in abortive DNA ligations |
? |
- |
? |
|
Organism
Organism |
UniProt |
Comment |
Textmining |
Homo sapiens |
Q7Z2E3 |
- |
- |
Reaction
Reaction |
Comment |
Organism |
Reaction ID |
adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA] + H2O = AMP + 5'-phospho-(ribonucleotide)-[DNA] |
the catalytic reaction proceeds in three steps: substrate protonation, DNA deadenylation and histidine-AMP intermediate hydrolysis. The calculated activation energies for the second and third reactions are 19.0 and 10.5 kcal/mol, which can be attributed to a penta-coordinated AMP-phosphoryl formation and closing of a water molecule, respectively. A histidine-AMP intermediate is hydrolyzed easily in the third step when a water molecule closes within 3 A to the phosphorus nucleus |
Homo sapiens |
|
adenosine-5'-diphospho-5'-[DNA] + H2O = AMP + phospho-5'-[DNA] |
the catalytic reaction proceeds in three steps: substrate protonation, DNA deadenylation and histidine-AMP intermediate hydrolysis. The calculated activation energies for the second and third reactions are 19.0 and 10.5 kcal/mol, which can be attributed to a penta-coordinated AMP-phosphoryl formation and closing of a water molecule, respectively. A histidine-AMP intermediate is hydrolyzed easily in the third step when a water molecule closes within 3 A to the phosphorus nucleus |
Homo sapiens |
|
Substrates and Products (Substrate)
Substrates |
Comment Substrates |
Organism |
Products |
Comment (Products) |
Rev. |
Reac. |
additional information |
aprataxin hydrolyses abnormal 5'-AMP DNA termini formed in abortive DNA ligations |
Homo sapiens |
? |
- |
? |
|
Synonyms
Synonyms |
Comment |
Organism |
aprataxin |
- |
Homo sapiens |
APTX |
- |
Homo sapiens |
General Information
General Information |
Comment |
Organism |
evolution |
aprataxin (APTX) belongs to a family of histidine triad (HIT) enzymes. Mutation of His138 to alanine does not completely abolish the catalytic activity; the residual activity is 25% of the wild-type enzyme activity. The DNA deadenylation reaction catalyzed by the H138A mutant can proceed by the protonated substrate |
Homo sapiens |
malfunction |
mutations of the APTX gene cause neurological diseases such as ataxia oculomotor aparaxia type 1 (AOA1) |
Homo sapiens |
additional information |
active site structure of APTX, and molecular reaction mechanism, modeling, overview. General acid-base catalysis of APTX with and important role of His138 as a general acid. The second step, the histidine-AMP intermediate hydrolysis, can proceed with the aid of the product DNA phosphate without a general base residue |
Homo sapiens |
physiological function |
5'-AMP DNA hydrolysis of aprataxin, energy profile of the APTX catalytic reaction and the protonate states, by quantum mechanical/molecular mechanical (QM/MM) calculations and modeling, overview. Aprataxin hydrolyses abnormal 5'-AMP DNA termini formed in abortive DNA ligations, it is an important DNA repair enzyme |
Homo sapiens |