| Autor: |
Sigman, Jeffrey A., Edwards, Sarah R., Pabon, Amanda, Glucksman, Marc J., Wolfson, Adele J. |
| Předmět: |
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| Zdroj: |
FEBS Letters; Jun2003, Vol. 545 Issue 2/3, p224, 5p |
| Abstrakt: |
Thimet oligopeptidase (EC 3.4.24.15; TOP) is a Zn(II) endopeptidase implicated in physiological regulation of processes involving neuropeptides. The present study clarifies the active site structure and mechanism of catalysis of TOP. The enzyme exhibited a bell-shaped pH dependence of activity having an acidic limb due to a protonation event with a pKa of 5.7 and a basic limb with pKa of 8.8. The acidic limb can be attributed to protonation of a residue affecting kcat while the alkaline limb may be due to conformational change. Mutation of Tyr612 to Phe resulted in more than 400-fold decrease in activity. This result, supported by modeling studies, implicates Tyr612 in transition state stabilization analogous to the role of His231 of thermolysin. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
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Plný text