Background: Streptococcus mutans pyrophosphatase (Sm-PPase) is a member of
a relatively uncommon but widely dispersed sequence family (family II) of i
norganic pyrophosphatases. A structure will answer two main questions: is i
t 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 crystallogr
aphy at 2.2 Angstrom resolution. The tertiary fold of Sm-PPase consists of
a 189 residue alpha/beta N-terminal domain and a 114 residue mixed beta she
et C-terminal domain and bears no resemblance to family I PPase, even thoug
h the arrangement of active site ligands and the residues that bind them sh
ows significant similarity. The preference for Mn2+ over Mg2+ in family II
PPases is explained by the histidine ligands and bidentate carboxylate coor
dination. The active site is located at the domain interface. The C-termina
l domain is hinged to the N-terminal domain and exists in both closed and o
pen conformations.
Conclusions: The active site similiarities, including a water coordinated t
o two metal ions, suggest that the family II PPase mechanism is "analogous"
(not "homologous") to that of family I PPases. This is a remarkable exampl
e of convergent evolution. The large change in C-terminal conformation sugg
ests that domain closure might be the mechanism by which Sm-PPase achieves
specificity for pyrophosphate over other polyphosphates.