1G0S

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

(2001) Nat Struct Biol 8: 467-472

• PubMed: 11323725 Search on PubMed
• DOI: https://doi.org/10.1038/87647
• Primary Citation of Related Structures:  
  1G0S, 1G9Q, 1GA7


• PubMed 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.

   View More

---

Organizational Affiliation: 

Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.