Literature summary for 4.2.99.B1 extracted from

Daskalova, S.M.; Bhattacharya, C.; Dedkova, L.M.; Hecht, S.M.
Probing the flexibility of the catalytic nucleophile in the lyase catalytic pocket of human DNA polymerase beta with unnatural lysine analogues (2017), Biochemistry, 56, 500-513 .

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Cloned(Commentary)

Cloned (Comment)	Organism
expression of mutant enzymes by coupled in vitro transcription and translation from a modified DNA template containing a TAG codon at the position corresponding to Lys72	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	the lyase catalytic pocket, Lys72, is replaced with each of several nonproteinogenic lysine analogues. The modified Pol beta enzymes are produced by coupled in vitro transcription and translation from a modified DNA template containing a TAG codon at the position corresponding to Lys72. In the presence of a misacylated tRNACUA transcript, suppression of the UAG codon in the transcribed mRNA leads to elaboration of full-length Pol beta having a lysine analogue at position 72. Replacement of the primary nucleophilic amine with a secondary amine in the form of N-methyllysine affects mainly the stability of the Schiff base intermediate and results in relatively moderate inhibition of lyase activity and BER. Elongation of the side chain of the catalytic residue by one methylene group, achieved by introduction of homolysine at position 72, apparently shifts the amino group to a position less favorable for Schiff base formation. This effect is attenuated when the side chain is elongated by replacing one side-chain methylene group with a bridging S atom (thialysine). In comparison, replacement of lysine 72 with an analogue having a guanidine moiety in lieu of an epsilon-amino group (homoarginine) or a sterically constrained secondary amine (piperidinylalanine) leads to almost complete suppression of dRP excision activity and the ability of Pol beta to support BER	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P06746	-	-

Synonyms

Synonyms	Comment	Organism
5'-deoxyribose phosphate lyase	-	Homo sapiens
5'-dRP lyase	-	Homo sapiens
DNA polymerase beta	-	Homo sapiens
pol beta	-	Homo sapiens

General Information

General Information	Comment	Organism
physiological function	DNA polymerase beta (Pol beta) is a key enzyme in mammalian base excision repair (BER), contributing stepwise 5'-deoxyribose phosphate (dRP) lyase and gap-filling DNA polymerase activities. The lyase reaction is believed to occur via a beta-elimination reaction following the formation of a Schiff base between the dRP group at the pre-incised apurinic/apyrimidinic site and the epsilon-amino group of Lys72	Homo sapiens

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Release 2023.1 (January 2023)