The structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family

Nat Struct Biol. 2001 May;8(5):467-72. doi: 10.1038/87647.

Abstract

Regulation of cellular levels of ADP-ribose is important in preventing nonenzymatic ADP-ribosylation of proteins. The Escherichia coli ADP-ribose pyrophosphatase, a Nudix enzyme, catalyzes the hydrolysis of ADP-ribose to ribose-5-P and AMP, compounds that can be recycled as part of nucleotide metabolism. The structures of the apo enzyme, the active enzyme and the complex with ADP-ribose were determined to 1.9 A, 2.7 A and 2.3 A, respectively. The structures reveal a symmetric homodimer with two equivalent catalytic sites, each formed by residues of both monomers, requiring dimerization through domain swapping for substrate recognition and catalytic activity. The structures also suggest a role for the residues conserved in each Nudix subfamily. The Nudix motif residues, folded as a loop-helix-loop tailored for pyrophosphate hydrolysis, compose the catalytic center; residues conferring substrate specificity occur in regions of the sequence removed from the Nudix motif. This segregation of catalytic and recognition roles provides versatility to the Nudix family.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Apoenzymes / chemistry
  • Apoenzymes / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Cations, Divalent / metabolism
  • Conserved Sequence
  • Crystallography, X-Ray
  • Dimerization
  • Enzyme Activation
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins*
  • Hydrolysis
  • Magnesium / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nudix Hydrolases
  • Phosphoric Monoester Hydrolases / chemistry
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein Structure, Tertiary
  • Pyrophosphatases / chemistry*
  • Pyrophosphatases / metabolism*
  • Sequence Alignment
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Apoenzymes
  • Bacterial Proteins
  • Cations, Divalent
  • Escherichia coli Proteins
  • Adenosine Diphosphate Ribose
  • Phosphoric Monoester Hydrolases
  • Pyrophosphatases
  • mutT protein, E coli
  • ADPribose pyrophosphatase
  • Magnesium

Associated data

  • PDB/1G0S
  • PDB/1G9Q
  • PDB/1GA7