Escherichia coli exonuclease III (ExoIII) and Neisseria meningitides NExo-like subfamily of the ExoIII family purinic/apyrimidinic (AP) endonucleases
This subfamily includes Escherichia coli ExoIII, Neisseria meningitides NExo,and related proteins. These are ExoIII family AP endonucleases and they belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. AP endonucleases participate in the DNA base excision repair (BER) pathway. AP sites are one of the most common lesions in cellular DNA. During BER, the damaged DNA is first recognized by DNA glycosylase. AP endonucleases then catalyze the hydrolytic cleavage of the phosphodiester bond 5' to the AP site, and this is followed by the coordinated actions of DNA polymerase, deoxyribose phosphatase, and DNA ligase. If left unrepaired, AP sites block DNA replication, and have both mutagenic and cytotoxic effects. AP endonucleases can carry out a variety of excision and incision reactions on DNA, including 3'-5' exonuclease, 3'-deoxyribose phosphodiesterase, 3'-phosphatase, and occasionally, nonspecific DNase activities. Different AP endonuclease enzymes catalyze the different reactions with different efficiencies. Many organisms have two AP endonucleases, usually one is the dominant AP endonuclease, the other has weak AP endonuclease activity. For example, Neisseria meningitides Nape and NExo, and exonuclease III (ExoIII) and endonuclease IV (EndoIV) in Escherichia coli. NExo and ExoIII are found in this subfamily. NExo is the non-dominant AP endonuclease. It exhibits strong 3'-5' exonuclease and 3'-deoxyribose phosphodiesterase activities. Escherichia coli ExoIII is an active AP endonuclease, and in addition, it exhibits double strand (ds)-specific 3'-5' exonuclease, exonucleolytic RNase H, 3'-phosphomonoesterase and 3'-phosphodiesterase activities, all catalyzed by a single active site. Class II AP endonucleases have been classified into two families, designated ExoIII and EndoIV, based on their homology to the Escherichia coli enzymes ExoIII and endonuclease IV (EndoIV). This subfamily belongs to the ExoIII family; the EndoIV family belongs to a different superfamily.
Comment:based on similarity to ExoIII-like AP endonuclease and other EEP superfamily members; compared with other EEP superfamily members, members of this family have a conserved Tyr residue is in place of a conserved His
Jiyao W et al.(2023). "The conserved domain database in 2023.",