Publication Abstract from PubMed
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.
Crystal structure of Streptococcus mutans pyrophosphatase: a new fold for an old mechanism.,Merckel MC, Fabrichniy IP, Salminen A, Kalkkinen N, Baykov AA, Lahti R, Goldman A Structure. 2001 Apr 4;9(4):289-97. PMID:11525166[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
