title: Drug targeting of heme proteins in Mycobacterium tuberculosis.
abstract: TB, caused by the human pathogen Mycobacterium tuberculosis (Mtb), causes more deaths than any other infectious disease. Iron is crucial for Mtb to infect the host and to sustain infection, with Mtb encoding large numbers of iron-binding proteins. Many of these are hemoproteins with key roles, including defense against oxidative stress, cellular signaling and regulation, host cholesterol metabolism, and respiratory processes. Various heme enzymes in Mtb are validated drug targets and/or products of genes essential for bacterial viability or survival in the host. Here, we review the structure, function, and druggability of key Mtb heme enzymes and strategies used for their inhibition.
authors.affiliation: School of Chemistry, The University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, UK.
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: McLean
authors.affiliation: School of Chemistry, The University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, UK. Electronic address: Andrew.Munro@Manchester.ac.uk.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Munro
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D006420:Hemeproteins