Literature summary for 4.2.99.B1 extracted from

Daskalova, S.M.; Bai, X.; Hecht, S.M.
Study of the lyase activity of human DNA polymerase beta using analogues of the intermediate Schiff base complex (2018), Biochemistry, 57, 2711-2722 .

Search for more literature for 4.2.99.B1

Cloned(Commentary)

Cloned (Comment)	Organism
codon-optimized gene POLB, recombinant expression of C-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site. The reaction mechanism of the lyase reaction involves a transient covalent enzyme-DNA intermediate in the form of a Schiff base connecting Lys72 of the enzyme with the 5'-dRP moiety. The Schiff base intermediate is resolved via a beta-elimination reaction, initiated by abstraction of a C2'-H atom from the 5'-deoxyribose phosphate (5'-dRP) moiety	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P06746	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant C-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli by immobilized-metal affinity chromatography and ultrafiltration	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
5'-deoxyribose phosphate DNA substrate	-	Homo sapiens	?	-	?
additional information	catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site. The reaction mechanism of the lyase reaction involves a transient covalent enzyme-DNA intermediate in the form of a Schiff base connecting Lys72 of the enzyme with the 5'-dRP moiety. The Schiff base intermediate is resolved via a beta-elimination reaction, initiated by abstraction of a C2'-H atom from the 5'-deoxyribose phosphate (5'-dRP) moiety	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
DNA polymerase beta	-	Homo sapiens
pol beta	-	Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	three Pol beta enzymes modified at position 72 with aminooxy or hydrazinyl analogues of lysine form transient covalent bonds with the 5'-dRP moiety of the damaged DNA, in the form of an oxime or hydrazone, respectively. Both types of enzyme DNA intermediates are ultimately resolved by the lyase activities of each of the modified enzymes. The formation and resolution of these E-S complexes proceed with diminished kinetics, and with an altered pH profile compared to wild-type. Comparison of base excision repair (BER) reaction with wild-type and modified Pol beta enzymes: while the wild-type enzyme performs BER very efficiently, the BER activity of the three modified enzymes is greatly reduced. The overall BER efficiency of our modified Pol beta enzymes reflects predominantly their ability to remove the 5'-dRP group, the modified proteins demonstrate poor lyase activity	Homo sapiens
additional information	study of the lyase activity of human DNA polymerase beta using analogues of the intermediate Schiff base complex	Homo sapiens
physiological function	DNA polymerase beta (Pol beta) participates in mammalian base excision repair (BER). The enzyme has a two-domain architecture, reflecting its dual functionality. The polymerase activity, which replaces damaged nucleosides removed during an initial excision process, is within the C-terminal 31 kDa domain, while the N-terminal 8 kDa domain participates in a lyase function, working to remove a 5'-deoxyribose phosphate (5'-dRP) moiety from the damaged DNA substrate	Homo sapiens

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Release 2023.1 (January 2023)