Crystal Structure of Streptococcus mutans Pyrophosphatase
| Autor: | Michael C. Merckel, Anu Salminen, Reijo Lahti, Nisse Kalkkinen, Adrian Goldman, Igor P. Fabrichniy, Alexander A. Baykov |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
0303 health sciences
Pyrophosphatase biology Chemistry Stereochemistry 030302 biochemistry & molecular biology Beta sheet Active site Pyrophosphate 03 medical and health sciences chemistry.chemical_compound Crystallography Structural Biology Hydrolase biology.protein Carboxylate Pyrophosphatases Molecular Biology Histidine 030304 developmental biology |
| Zdroj: | Structure. 9(4):289-297 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/s0969-2126(01)00587-1 |
| Popis: | 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 α/β N-terminal domain and a 114 residue mixed β 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 Mn 2+ over Mg 2+ 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. |
| Databáze: | OpenAIRE |
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