Effects of Compatible Solutes on Mammalian Cytochrome P450 Stability

Abstract

Abstract The sensitivity of pig cytochrome P450cl7 (CYP17), an endoplasmic reticulum membrane-bound enzyme, towards heat denaturation (48 °C) was measured by the P450-to-P420 spectral transition indicating conforma­tional labilization of the protein. Both sucrose and glucose have comparable and increasingly protective effects at concentrations ranging from 100 to 800 mм, while ectoine, a novel zwitterionic compatible solute which regulates bacterial osmoadaptation and stabilizes cytoplasmic enzymes, has a strong labilizing effect on CYP17 and favours its proteolytic inactivation possibly by electrostatic derangements. Sucrose or glucose, but not ectoine, can therefore eventually be proposed as compatible stabilizers of cytochrome P450 structures.