The tuberculosis necrotizing toxin is an NAD⁺ and NADP⁺ glycohydrolase with distinct enzymatic properties.

ABSTRACT: Upon host infection, Mycobacterium tuberculosis secretes the tuberculosis necrotizing toxin (TNT) into the cytosol of infected macrophages, leading to host cell death by necroptosis. TNT hydrolyzes NAD⁺ in the absence of any exogenous cofactor, thus classifying it as a β-NAD⁺ glycohydrolase. However, TNT lacks sequence similarity with other NAD⁺ hydrolyzing enzymes and lacks the essential motifs involved in NAD⁺ binding and hydrolysis by these enzymes. In this study, we used NMR to examine the enzymatic activity of TNT and found that TNT hydrolyzes NADP⁺ as fast as NAD⁺ but does not cleave the corresponding reduced dinucleotides. This activity of TNT was not inhibited by ADP-ribose or nicotinamide, indicating low affi

SUBMITTER: Tak U 

PROVIDER: S-EPMC6398120 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature