title: Structures of an ATP-independent Lon-like protease and its complexes with covalent inhibitors.
abstract: The Lon proteases are a unique family of chambered proteases with a built-in AAA+ (ATPases associated with diverse cellular activities) module. Here, crystal structures of a unique member of the Lon family with no intrinsic ATPase activity in the proteolytically active form are reported both alone and in complexes with three covalent inhibitors: two peptidomimetics and one derived from a natural product. This work reveals the unique architectural features of an ATP-independent Lon that selectively degrades unfolded protein substrates. Importantly, these results provide mechanistic insights into the recognition of inhibitors and polypeptide substrates within the conserved proteolytic chamber, which may aid the development of specific Lon-protease inhibitors.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Jiahn-Haur
authors.initials: JH
authors.lastname: Liao
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ihara
authors.forename: Chiao-I
authors.initials: CI
authors.lastname: Kuo
authors.forename: Kai-Fa
authors.initials: KF
authors.lastname: Huang
authors.forename: Soichi
authors.initials: S
authors.lastname: Wakatsuki
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Chang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001897:Boronic Acids / Q000737:chemistry / Q000378:metabolism; D000069286:Bortezomib; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D034301:Deinococcus / Q000201:enzymology; D007783:Lactones / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D049070:Protease La / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D011719:Pyrazines / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001897:Boronic Acids; D007783:Lactones; D011480:Protease Inhibitors; D011719:Pyrazines; C117645:omuralide; D000069286:Bortezomib; D000255:Adenosine Triphosphate; D049070:Protease La
keywords: Lon proteases; LonC; inhibitors