Crystal structure of Streptococcus mutans pyrophosphatase: a new fold for an old mechanism.
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.
Merckel
M C
MC
Institute of Biotechnology, University of Helsinki, Finland.
Fabrichniy
I P
IP
Salminen
A
A
Kalkkinen
N
N
Baykov
A A
AA
Lahti
R
R
Goldman
A
A
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*
D008024:Ligands; D011755:Pyrophosphatases