Evidence for a Structure-Function Relationship in the Activation of Calcineurin by Metal Ions

✍ Scribed by Bruce L Martin

• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 181 KB
• Volume: 28
• Category: Article
• ISSN: 0045-2068
• DOI: 10.1006/bioo.1999.1154

✦ Synopsis

Kinetic parameters for the metal ion activation of calcineurin at 30°C were found to be correlated to the formation constants (log K 1 ) of the activating metal ions (Mn 2+ , Co 2+ , Ni 2+ , Zn 2+ , and Mg 2+ ) with the substrate para-nitrophenyl phosphate (pNPP). Metal ion activation measured by k cat /K act increased with increasing formation constant, although this correlation failed to explain the lack of activation by other metal ions having similar formation constants with pNPP, Ca 2+ , and Sr 2+ , for example. An empirical model describing metal ion activation was developed by inclusion of another constant for the metal ions, the hydrolysis constant (pK a M-H 2 O) of water coordinated to the metal ion with an increase in the pK a related to decreasing activation. The resulting two parameter equation improved the relationship between metal ion properties and enzyme activation. Nonactivating metal ions have the highest values of pK a providing a possible explanation for their failure to cause activation. Derivation of the two-parameter equation inferred that the two properties of metal ions may be important determinants of the role(s) of exogenous metal ion in calcineurin catalysis.