title: Crystal structure of Streptococcus mutans pyrophosphatase: a new fold for an old mechanism.
abstract: BACKGROUND
  Streptococcus mutans pyrophosphatase (Sm-PPase) is a member of a relatively uncommon but widely dispersed sequence family (family II) of inorganic pyrophosphatases. A structure will answer two main questions: is it structurally similar to the family I PPases, and is the mechanism similar?
  
  
  RESULTS
  The first family II PPase structure, that of homodimeric Sm-PPase complexed with metal and sulfate ions, has been solved by X-ray crystallography at 2.2 A resolution. The tertiary fold of Sm-PPase consists of a 189 residue alpha/beta N-terminal domain and a 114 residue mixed beta sheet C-terminal domain and bears no resemblance to family I PPase, even though the arrangement of active site ligands and the residues that bind them shows significant similarity. The preference for Mn2+ over Mg2+ in family II PPases is explained by the histidine ligands and bidentate carboxylate coordination. The active site is located at the domain interface. The C-terminal domain is hinged to the N-terminal domain and exists in both closed and open conformations.
  
  
  CONCLUSIONS
  The active site similiarities, including a water coordinated to two metal ions, suggest that the family II PPase mechanism is "analogous" (not "homologous") to that of family I PPases. This is a remarkable example of convergent evolution. The large change in C-terminal conformation suggests that domain closure might be the mechanism by which Sm-PPase achieves specificity for pyrophosphate over other polyphosphates.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: M C
authors.initials: MC
authors.lastname: Merckel
authors.forename: I P
authors.initials: IP
authors.lastname: Fabrichniy
authors.forename: A
authors.initials: A
authors.lastname: Salminen
authors.forename: N
authors.initials: N
authors.lastname: Kalkkinen
authors.forename: A A
authors.initials: AA
authors.lastname: Baykov
authors.forename: R
authors.initials: R
authors.lastname: Lahti
authors.forename: A
authors.initials: A
authors.lastname: Goldman
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D008024:Ligands; D013058:Mass Spectrometry; D008958:Models, Molecular; D018583:Pliability; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011755:Pyrophosphatases / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013295:Streptococcus mutans / Q000201:enzymology*
chemical_list: D008024:Ligands; D011755:Pyrophosphatases