Activating Compound | Comment | Organism | Structure |
---|---|---|---|
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 |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
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 | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
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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 | ? | - |
? | |
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 | ? | - |
? | |
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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Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | P96273 | - |
- |
Mycobacterium tuberculosis ATCC 25618 | P96273 | - |
- |
Mycobacterium tuberculosis H37Rv | P96273 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
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 | ? | - |
? | |
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 | ? | - |
? | |
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 | ? | - |
? | |
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 | ? | - |
? | |
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 | ? | - |
? | |
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 | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
class II apurinic/apyrimidinic-endonuclease/3'-5' exonuclease III | - |
Mycobacterium tuberculosis |
class-II AP-endonuclease | - |
Mycobacterium tuberculosis |
MtbXthA | - |
Mycobacterium tuberculosis |
xthA | - |
Mycobacterium tuberculosis |
General Information | Comment | Organism |
---|---|---|
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 |
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 |