title: N,C-Capped dipeptides with selectivity for mycobacterial proteasome over human proteasomes: role of S3 and S1 binding pockets.
abstract: We identified N,C-capped dipeptides that are selective for the Mycobacterium tuberculosis proteasome over human constitutive and immunoproteasomes. Differences in the S3 and S1 binding pockets appeared to account for the species selectivity. The inhibitors can penetrate mycobacteria and kill nonreplicating M. tuberculosis under nitrosative stress.
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. gal2005@med.cornell.edu
authors.forename: Gang
authors.initials: G
authors.lastname: Lin
authors.forename: Tamutenda
authors.initials: T
authors.lastname: Chidawanyika
authors.forename: Christopher
authors.initials: C
authors.lastname: Tsu
authors.forename: Thulasi
authors.initials: T
authors.lastname: Warrier
authors.forename: Julien
authors.initials: J
authors.lastname: Vaubourgeix
authors.forename: Christopher
authors.initials: C
authors.lastname: Blackburn
authors.forename: Kenneth
authors.initials: K
authors.lastname: Gigstad
authors.forename: Michael
authors.initials: M
authors.lastname: Sintchak
authors.forename: Lawrence
authors.initials: L
authors.lastname: Dick
authors.forename: Carl
authors.initials: C
authors.lastname: Nathan
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D046988:Proteasome Endopeptidase Complex