{"metadata":{"accession":"PF14021","entry_id":null,"type":"domain","go_terms":null,"source_database":"pfam","member_databases":null,"integrated":"IPR025331","hierarchy":null,"name":{"name":"Tuberculosis necrotizing toxin","short":"TNT"},"description":[{"text":"<p>This is the C-terminal domain secreted by Mycobacterium tuberculosis (Mtb). It induces necrosis of infected cells to evade immune responses. Mtb utilizes the protein CpnT to kill human macrophages by secreting its C-terminal domain (CTD), named tuberculosis necrotizing toxin (TNT) that induces necrosis. It acts as a NAD+ glycohydrolase which hydrolyzes the essential cellular coenzyme NAD+ in the cytosol of infected macrophages resulting in necrotic cell death [[cite:PUB00082601]]. CpnT transports its toxic CTD from the cell surface of M. tuberculosis by proteolytic cleavage, where the toxin is cleaved to induce host cell death [[cite:PUB00082600]]. Structural analysis determined that the TNT core contains only six beta-strands as opposed to seven found in all known NAD+-utilizing toxins, and is significantly smaller, with only two short alpha-helices and two 3/10 helices. Furthermore, the putative NAD+ binding pocket identified Q822, Y765 and R757 as residues possibly involved in NAD+-binding and hydrolysis based on similar positions of catalytic amino acids of ADP-ribosylating toxins. While glutamine 822 residue was detected to be highly conserved among TNT homologs [[cite:PUB00082601]].</p>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00082601":{"PMID":26237511,"ISBN":null,"volume":"22","issue":"9","year":2015,"title":"The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.","URL":null,"raw_pages":"672-8","medline_journal":"Nat Struct Mol Biol","ISO_journal":"Nat. Struct. Mol. Biol.","authors":["Sun J","Siroy A","Lokareddy RK","Speer A","Doornbos KS","Cingolani G","Niederweis M."],"DOI_URL":"http://dx.doi.org/10.1038/nsmb.3064"},"PUB00082600":{"PMID":24753609,"ISBN":null,"volume":"111","issue":"18","year":2014,"title":"An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity.","URL":null,"raw_pages":"6750-5","medline_journal":"Proc Natl Acad Sci U S A","ISO_journal":"Proc. Natl. Acad. Sci. U.S.A.","authors":["Danilchanka O","Sun J","Pavlenok M","Maueroder C","Speer A","Siroy A","Marrero J","Trujillo C","Mayhew DL","Doornbos KS","Munoz LE","Herrmann M","Ehrt S","Berens C","Niederweis M."],"DOI_URL":"http://dx.doi.org/10.1073/pnas.1400136111"}},"set_info":{"accession":"CL0084","name":"ADP-ribosyl"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":109,"interactions":0,"matches":2676,"pathways":0,"proteins":2673,"proteomes":1695,"sets":1,"structural_models":{"alphafold":1685},"structures":8,"taxa":2848},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":82,"alignment:full":1349},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":null}}