title: Crystal structure of dinitrogenase reductase-activating glycohydrolase (DraG) reveals conservation in the ADP-ribosylhydrolase fold and specific features in the ADP-ribose-binding pocket.
abstract: Protein-reversible ADP-ribosylation is emerging as an important post-translational modification used to control enzymatic and protein activity in different biological systems. This modification regulates nitrogenase activity in several nitrogen-fixing bacterial species. ADP-ribosylation is catalyzed by ADP-ribosyltransferases and is reversed by ADP-ribosylhydrolases. The structure of the ADP-ribosylhydrolase that acts on Azospirillum brasilense nitrogenase (dinitrogenase reductase-activating glycohydrolase, DraG) has been solved at a resolution of 2.5 A. This bacterial member of the ADP-ribosylhydrolase family acts specifically towards a mono-ADP-ribosylated substrate. The protein shows an all-alpha-helix structure with two magnesium ions located in the active site. Comparison of the DraG structure with orthologues deposited in the Protein Data Bank from Archaea and mammals indicates that the ADP-ribosylhydrolase fold is conserved in all domains of life. Modeling of the binding of the substrate ADP-ribosyl moiety to DraG is in excellent agreement with biochemical data.
authors.affiliation: Biomolecular Research, Paul Scherrer Institut, Villigen, Switzerland.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Li
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Huergo
authors.forename: Antonietta
authors.initials: A
authors.lastname: Gasperina
authors.forename: Fábio O
authors.initials: FO
authors.lastname: Pedrosa
authors.forename: Mike
authors.initials: M
authors.lastname: Merrick
authors.forename: Fritz K
authors.initials: FK
authors.lastname: Winkler
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism; D015806:Azospirillum brasilense / Q000201:enzymology*; D001665:Binding Sites; D002413:Cations, Divalent; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000737:chemistry* / Q000378:metabolism; D009586:Nitrogen Fixation; D011485:Protein Binding; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D019843:Archaeal Proteins; D002413:Cations, Divalent; D000246:Adenosine Diphosphate Ribose; D009699:N-Glycosyl Hydrolases; C046422:ADP-ribosylarginine hydrolase; C036091:ADP-ribosyl-(dinitrogen reductase) hydrolase; D008274:Magnesium