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Literature summary for 2.7.4.6 extracted from

  • Sun, J.; Singh, V.; Lau, A.; Stokes, R.W.; Obregon-Henao, A.; Orme, I.M.; Wong, D.; Av-Gay, Y.; Hmama, Z.
    Mycobacterium tuberculosis nucleoside diphosphate kinase inactivates small GTPases leading to evasion of innate immunity (2013), PLoS Pathog., 9, e1003499.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.4.6

Protein Variants

Protein Variants Comment Organism
additional information antisense knockdown of nucleoside diphosphate kinase, the stable mutant Mtb Ndk-AS displays attenuated intracellular survival along with reduced persistence in the lungs of infected mice. In the generated mutant strain Mtb Ndk-AS the Ndk protein expression is undetectable. ROS production is inhibited in the presence of Mtb Ndk Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Mycobacterium tuberculosis the enzyme binds to and inactivates the small GTPase Rac1 in the macrophage. This results in the exclusion of the Rac1 binding partner p67phox from phagosomes containing bacteria- or enzyme-coated latex beads. Exclusion of p67phox is associated with a defect of both NOX2 assembly and production of reactive oxygen species in response to wild-type bacteria ?
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Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis
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 gene ndk
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the enzyme binds to and inactivates the small GTPase Rac1 in the macrophage. This results in the exclusion of the Rac1 binding partner p67phox from phagosomes containing bacteria- or enzyme-coated latex beads. Exclusion of p67phox is associated with a defect of both NOX2 assembly and production of reactive oxygen species in response to wild-type bacteria Mycobacterium tuberculosis ?
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 ?

Synonyms

Synonyms Comment Organism
NDK
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 Mycobacterium tuberculosis
nucleoside diphosphate kinase
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 Mycobacterium tuberculosis

General Information

General Information Comment Organism
malfunction the stable knockout mutant Mtb Ndk-AS displays attenuated intracellular survival along with reduced persistence in the lungs of infected mice. Mutant Mtb Ndk-AS, which lost the capacity to disrupt Rac1-p67phox interaction, induces a strong ROS production. Given the established link between NOX2 activation and apoptosis, the proportion of Annexin V positive cells and levels of intracellular active caspase 3 are significantly higher in cells infected with Mtb Ndk-AS compared to wild-type Mtb. Knockdown of Ndk converts Mtb into a pro-apoptotic mutant strain that has a phenotype of increased susceptibility to intracellular killing and reduced virulence in vivo, phenotype, overview. Disruption of Ndk expression converts Mtb into a mutant strain that induces strong ROS and apoptosis responses. This phenotype is associated with reduced survival of Ndk mutant in vitro and in vivo Mycobacterium tuberculosis
physiological function the enzyme is involved in the mechanism of Mycobacterium tuberculosis persistence in the host macrophage and inactivates small GTPases leading to evasion of innate immunity. Nucleoside diphosphate kinase contributes to phagosome maturation arrest via inactivation of Rab5 and Rab7. Ndk also targets and inactivates the small GTPase Rac1, an essential component of the macrophage NADPH oxidase (NOX2) complex. Ndk-dependent inactivation of Rac1 is associated with reduced NOX2-mediated production of reactive oxygen species (ROS) and ROS-dependent apoptosis. Ndk-mediated inhibition of ROS reduces the macrophage killing capability. The organism uses Ndk as GAP activity towards macrophage Rac1 Mycobacterium tuberculosis