Crystal structure of Streptococcus mutans pyrophosphatase: A new fold for an old mechanism

Citation
Mc. Merckel et al., Crystal structure of Streptococcus mutans pyrophosphatase: A new fold for an old mechanism, STRUCTURE, 9(4), 2001, pp. 289-297
Citations number
28
Categorie Soggetti
Biochemistry & Biophysics
Journal title
STRUCTURE
ISSN journal
09692126 → ACNP
Volume
9
Issue
4
Year of publication
2001
Pages
289 - 297
Database
ISI
SICI code
0969-2126(20010407)9:4<289:CSOSMP>2.0.ZU;2-9
Abstract
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.