title: Regulation of nitrogenase by reversible mono-ADP-ribosylation.
abstract: Posttranslational modification of proteins plays a key role in the regulation of a plethora of metabolic functions. Protein modification by mono-ADP-ribosylation was first described as a mechanism of action of bacterial toxins. Since these pioneering studies, the number of pathways regulated by ADP-ribosylation in organisms from all domains of life expanded significantly. However, in only a few cases the full regulatory ADP-ribosylation circuit is known. Here, we review the system where mono-ADP-ribosylation regulates the activity of an enzyme: the regulation of nitrogenase in bacteria. When the nitrogenase product, ammonium, becomes available, the ADP-ribosyltransferase (DraT) covalently links an ADP-ribose moiety to a specific arginine residue on nitrogenase switching-off nitrogenase activity. After ammonium exhaustion, the ADP-ribosylhydrolase (DraG) removes the modifying group, restoring nitrogenase activity. DraT and DraG activities are reversibly regulated through interaction with PII signaling proteins . Bioinformatics analysis showed that DraT homologs are restricted to a few nitrogen-fixing bacteria while DraG homologs are widespread in Nature. Structural comparisons indicated that bacterial DraG is closely related to Archaea and mammalian ADP-ribosylhydrolases (ARH). In all available structures, the ARH active site consists of a hydrophilic cleft carrying a binuclear Mg(2+) or Mn(2+) cluster, which is critical for catalysis.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia da Fixação Biológica de Nitrogênio, Departamento de Bioquímica e Biologia Molecular, UFPR, Curitiba, PR, Brazil.
authors.forename: Vivian R
authors.initials: VR
authors.lastname: Moure
authors.forename: Flavia F
authors.initials: FF
authors.lastname: Costa
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Cruz
authors.forename: Fabio O
authors.initials: FO
authors.lastname: Pedrosa
authors.forename: Emanuel M
authors.initials: EM
authors.lastname: Souza
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Li
authors.forename: Fritz
authors.initials: F
authors.lastname: Winkler
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Huergo
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056890:Eukaryota / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009591:Nitrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D001426:Bacterial Proteins; D000246:Adenosine Diphosphate Ribose; D009591:Nitrogenase; D036002:ADP Ribose Transferases