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Literature summary extracted from

  • Khanam, T.; Rai, N.; Ramachandran, R.
    Mycobacterium tuberculosis class II apurinic/apyrimidinic-endonuclease/3'-5' exonuclease III exhibits DNA regulated modes of interaction with the sliding DNA beta-clamp (2015), Mol. Microbiol., 98, 46-68 .
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
3.1.11.2 additional information the sliding DNA beta-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. The beta-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity. Additionally, loading of the beta-clamp onto DNA is required for activity stimulation. Reduction in XthA activity stimulation is observed in the presence of beta-clamp binding peptides supporting that direct interactions between the proteins are necessary to cause stimulation. The inclusion of beta-clamp in the reaction mixture substantially enhanced the exonuclease activity with an about 8fold stimulation in the hydrolysis of the labelled strand Mycobacterium tuberculosis
4.2.99.18 additional information the sliding DNA beta-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. The beta-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity, with an approximate ninefold augmentation in AP site incision activity at the highest concentration of beta-clamp. Additionally, loading of the beta-clamp onto DNA is required for activity stimulation. Reduction in XthA activity stimulation is observed in the presence of beta-clamp binding peptides supporting that direct interactions between the proteins are necessary to cause stimulation Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.1.11.2 additional information while a clamp-specific inhibitor can disrupt the beta-clamp-XthA complex, a proliferating cell nuclear antigen (PCNA)-specific inhibitor is not able to do so Mycobacterium tuberculosis
4.2.99.18 additional information while a clamp-specific inhibitor can disrupt the beta-clamp-XthA complex, a proliferating cell nuclear antigen (PCNA)-specific inhibitor is not able to do so Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.1.11.2 additional information Mycobacterium tuberculosis MtbXthA is a versatile enzyme withAP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview ?
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 ?
3.1.11.2 additional information Mycobacterium tuberculosis H37Rv MtbXthA is a versatile enzyme withAP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview ?
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 ?
3.1.11.2 additional information Mycobacterium tuberculosis ATCC 25618 MtbXthA is a versatile enzyme withAP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview ?
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 ?
4.2.99.18 additional information Mycobacterium tuberculosis MtbXthA is a versatile enzyme with AP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview ?
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 ?
4.2.99.18 additional information Mycobacterium tuberculosis H37Rv MtbXthA is a versatile enzyme with AP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview ?
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 ?
4.2.99.18 additional information Mycobacterium tuberculosis ATCC 25618 MtbXthA is a versatile enzyme with AP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview ?
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 ?

Organism

EC Number Organism UniProt Comment Textmining
3.1.11.2 Mycobacterium tuberculosis P96273
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3.1.11.2 Mycobacterium tuberculosis ATCC 25618 P96273
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3.1.11.2 Mycobacterium tuberculosis H37Rv P96273
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4.2.99.18 Mycobacterium tuberculosis P96273
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4.2.99.18 Mycobacterium tuberculosis ATCC 25618 P96273
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4.2.99.18 Mycobacterium tuberculosis H37Rv P96273
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Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.11.2 DNA duplex X1 + H2O MtbXthA possesses a 3'-5' exonuclease activity on 3' recessed duplex DNA, substrate is 5'-FAM peptide-labelled 3'-recessed DNA duplex substrate X1. The incubation of substrate X1 with restrictive concentration of purified MtbXthAalone resulted in only 11% cleavage generating shorter-labelled oligomers. The inclusion of beta-clamp in the reaction mixture substantially enhances the exonuclease activity Mycobacterium tuberculosis ?
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 ?
3.1.11.2 DNA duplex X1 + H2O MtbXthA possesses a 3'-5' exonuclease activity on 3' recessed duplex DNA, substrate is 5'-FAM peptide-labelled 3'-recessed DNA duplex substrate X1. The incubation of substrate X1 with restrictive concentration of purified MtbXthAalone resulted in only 11% cleavage generating shorter-labelled oligomers. The inclusion of beta-clamp in the reaction mixture substantially enhances the exonuclease activity Mycobacterium tuberculosis H37Rv ?
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 ?
3.1.11.2 DNA duplex X1 + H2O MtbXthA possesses a 3'-5' exonuclease activity on 3' recessed duplex DNA, substrate is 5'-FAM peptide-labelled 3'-recessed DNA duplex substrate X1. The incubation of substrate X1 with restrictive concentration of purified MtbXthAalone resulted in only 11% cleavage generating shorter-labelled oligomers. The inclusion of beta-clamp in the reaction mixture substantially enhances the exonuclease activity Mycobacterium tuberculosis ATCC 25618 ?
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 ?
3.1.11.2 additional information MtbXthA is a versatile enzyme withAP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview Mycobacterium tuberculosis ?
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 ?
3.1.11.2 additional information MtbXthA is a versatile enzyme withAP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview Mycobacterium tuberculosis H37Rv ?
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 ?
3.1.11.2 additional information MtbXthA is a versatile enzyme withAP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview Mycobacterium tuberculosis ATCC 25618 ?
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 ?
4.2.99.18 additional information MtbXthA is a versatile enzyme with AP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview Mycobacterium tuberculosis ?
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 ?
4.2.99.18 additional information approximate ninefold augmentation in AP site incision activity at the highest concentration of beta-clamp used. Additionally, marked increase in the generation of shorter oligonucleotide fragments, smaller than 32-mer, is observed due to exonucleolytic excision of nucleotides from the 32 nucleotide oligomer Mycobacterium tuberculosis ?
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 ?
4.2.99.18 additional information MtbXthA is a versatile enzyme with AP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview Mycobacterium tuberculosis H37Rv ?
-
 ?
4.2.99.18 additional information approximate ninefold augmentation in AP site incision activity at the highest concentration of beta-clamp used. Additionally, marked increase in the generation of shorter oligonucleotide fragments, smaller than 32-mer, is observed due to exonucleolytic excision of nucleotides from the 32 nucleotide oligomer Mycobacterium tuberculosis H37Rv ?
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 ?
4.2.99.18 additional information MtbXthA is a versatile enzyme with AP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. XthA forms in vivo and in vitro complexes with beta-clamp DNA, the DNA substrate mediates different interaction modes between XthA and the beta-clamp, mechanism and structure, detailed overview Mycobacterium tuberculosis ATCC 25618 ?
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 ?
4.2.99.18 additional information approximate ninefold augmentation in AP site incision activity at the highest concentration of beta-clamp used. Additionally, marked increase in the generation of shorter oligonucleotide fragments, smaller than 32-mer, is observed due to exonucleolytic excision of nucleotides from the 32 nucleotide oligomer Mycobacterium tuberculosis ATCC 25618 ?
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 ?

Synonyms

EC Number Synonyms Comment Organism
3.1.11.2 class II apurinic/apyrimidinic-endonuclease/3'-5' exonuclease III
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 Mycobacterium tuberculosis
3.1.11.2 class-II AP-endonuclease
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 Mycobacterium tuberculosis
3.1.11.2 MtbXthA
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 Mycobacterium tuberculosis
3.1.11.2 xthA
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 Mycobacterium tuberculosis
4.2.99.18 class-II AP-endonuclease
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 Mycobacterium tuberculosis
4.2.99.18 MtbXthA
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 Mycobacterium tuberculosis
4.2.99.18 xthA
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 Mycobacterium tuberculosis

General Information

EC Number General Information Comment Organism
3.1.11.2 additional information the PIP motif mediates critical interactions between AP endonuclease and proliferating cell nuclear antigen (PCNA), both in vitro and in vivo. The PIP motif in PCNA-interacting proteins is a defined consensus sequence (QxxLxxFF), while the consensus sequence corresponding to the beta-clamp interacting motif in prokaryotes is relatively less conserved. Structure comparison of homodimeric mycobacterial beta-clamp and homotrimeric human PCNA, overview Mycobacterium tuberculosis
3.1.11.2 physiological function MtbXthA is a versatile enzyme withAP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. the sliding DNA beta-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. A novel 239QLRFPKK245 motif in the DNA-binding domain of XthA is found to be important for the interactions. Likewise, the peptide binding-groove (PBG) and the C-terminal of beta-clamp located on different domains interact with XthA. The beta-clamp-XthA complex can be disrupted by clamp binding peptides and also by a specific bacterial clamp inhibitor that binds at the PBG. Addition of beta-clamp binding peptides disrupts the MtbXthA-clamp complex and inhibits clamp-dependent stimulation of MtbXthA, overview. The beta-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity. Additionally, loading of the beta-clamp onto DNA is required for activity stimulation. In the absence of DNA, the PBG located on the second domain of the beta-clamp is important for interactions with XthA, while the C-terminal domain predominantly mediates functional interactions in the substrate's presence. The C-terminal domain of beta-clamp predominantly mediates interactions with XthA in the presence of DNA Mycobacterium tuberculosis
4.2.99.18 additional information the PIP motif mediates critical interactions between AP endonuclease and proliferating cell nuclear antigen (PCNA), both in vitro and in vivo. The PIP motif in PCNA-interacting proteins is a defined consensus sequence (QxxLxxFF), while the consensus sequence corresponding to the beta-clamp interacting motif in prokaryotes is relatively less conserved. Structure comparison of homodimeric mycobacterial beta-clamp and homotrimeric human PCNA, overview Mycobacterium tuberculosis
4.2.99.18 physiological function MtbXthA is a versatile enzyme with AP endonuclease, 3'-5' exonuclease and 3' phosphodiesterase activities. the sliding DNA beta-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. A novel 239QLRFPKK245 motif in the DNA-binding domain of XthA is found to be important for the interactions. Likewise, the peptide binding-groove (PBG) and the C-terminal of beta-clamp located on different domains interact with XthA. The beta-clamp-XthA complex can be disrupted by clamp binding peptides and also by a specific bacterial clamp inhibitor that binds at the PBG. Addition of beta-clamp binding peptides disrupts the MtbXthA-clamp complex and inhibits clamp-dependent stimulation of MtbXthA, overview. In the AP incision activities, the control experiments involving a random peptide had no effect on activity stimulation, while addition of peptides derived from alpha subunit, delta subunit, and MtbXthA, respectively, result in 2.0-2.5fold decreased stimulation of MtbXthA activity. The beta-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity. Additionally, loading of the beta-clamp onto DNA is required for activity stimulation. In the absence of DNA, the PBG located on the second domain of the beta-clamp is important for interactions with XthA, while the C-terminal domain predominantly mediates functional interactions in the substrate's presence. The C-terminal domain of beta-clamp predominantly mediates interactions with XthA in the presence of DNA Mycobacterium tuberculosis