title: Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6.
abstract: Bleomycin hydrolase is a cysteine protease that hydrolyzes the anticancer drug bleomycin. The homolog in yeast, Gal6, has recently been identified and found to bind DNA and to act as a repressor in the Gal4 regulatory system. The crystal structure of Gal6 at 2.2 A resolution reveals a hexameric structure with a prominent central channel. The papain-like active sites are situated within the central channel, in a manner resembling the organization of active sites in the proteasome. The Gal6 channel is lined with 60 lysine residues from the six subunits, suggesting a role in DNA binding. The carboxyl-terminal arm of Gal6 extends into the active site cleft and may serve a regulatory function. Rather than each residing in distinct, separable domains, the protease and DNA-binding activities appear structurally intertwined in the hexamer, implying a coupling of these two activities.
authors.affiliation: Divison of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
authors.forename: L
authors.initials: L
authors.lastname: Joshua-Tor
authors.forename: H E
authors.initials: HE
authors.lastname: Xu
authors.forename: S A
authors.initials: SA
authors.lastname: Johnston
authors.forename: D C
authors.initials: DC
authors.lastname: Rees
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D004247:DNA; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase