Biochemistry of C3 and related thiolester proteins in infection and inflammation

The characterization of the reactive thiolester bond in the third component of human complement has led to the identification of homologous sites in a number of proteins. In addition to the participation of the C3 thiolester in the opsonic acylation of surface components of microorganisms, new evidence is emerging to implicate thiolester disruption by physiologic nucleophiles, such as ammonia, as a potent mediator of local inflammation in the lung, the kidney, and at endothelial surfaces. Manipulation of the thiolester bonds in these related proteins should permit us to understand, and ultimately to direct, the molecular mechanisms of inflammation.