title: Mycobacterium tuberculosis prokaryotic ubiquitin-like protein-deconjugating enzyme is an unusual aspartate amidase.
abstract: Deamidase of Pup (Dop), the prokaryotic ubiquitin-like protein (Pup)-deconjugating enzyme, is critical for the full virulence of Mycobacterium tuberculosis and is unique to bacteria, providing an ideal target for the development of selective chemotherapies. We used a combination of genetics and chemical biology to characterize the mechanism of depupylation. We identified an aspartate as a potential nucleophile in the active site of Dop, suggesting a novel protease activity to target for inhibitor development.
authors.affiliation: Department of Microbiology, New York University, New York, New York 10016, USA.
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Burns
authors.forename: Fiona E
authors.initials: FE
authors.lastname: McAllister
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwerdtfeger
authors.forename: Julian
authors.initials: J
authors.lastname: Mintseris
authors.forename: Francisca
authors.initials: F
authors.lastname: Cerda-Maira
authors.forename: Elke E
authors.initials: EE
authors.lastname: Noens
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
authors.forename: Stevan R
authors.initials: SR
authors.lastname: Hubbard
authors.forename: Francesco
authors.initials: F
authors.lastname: Melandri
authors.forename: Huib
authors.initials: H
authors.lastname: Ovaa
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: K Heran
authors.initials: KH
authors.lastname: Darwin
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000235:genetics; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D055162:Biocatalysis; D020134:Catalytic Domain; D003980:Diazooxonorleucine / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry; D006868:Hydrolysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D003980:Diazooxonorleucine; D000581:Amidohydrolases