Cellular Disulfide Bond Formation in Bioactive Peptides and Proteins

Cellular Disulfide Bond Formation in Bioactive Peptides and Proteins

Bioactive peptides play important roles in metabolic regulation and modulation and many are used as therapeutics. These peptides often possess disulfide bonds, which are important for their structure, function and stability. A systematic network of enzymes--a disulfide bond generating enzyme, a disulfide bond donor enzyme and a redox cofactor--that function inside the cell dictates the formatio...

Native disulfide bond formation in proteins.

Native disulfide bond formation is critical for the proper folding of many proteins. Recent studies using newly identified protein oxidants, folding catalysts, and mutant cells provide insight into the mechanism of oxidative protein folding in vivo. This insight promises new strategies for more efficient protein production.

Formation of disulfide bonds in synthetic peptides and proteins.

Conservation and diversity of the cellular disulfide bond formation pathways.

Two pathways for the formation of biosynthetic protein disulfide bonds have been characterized in the endoplasmic reticulum (ER) of eukaryotes. In the major pathway, the membrane-associated flavoprotein Ero1 generates disulfide bonds for transfer to protein disulfide isomerase (PDI), which is responsible for directly introducing disulfide bonds into secretory proteins. In a minor fungal-specifi...

Small-molecule Catalysis of Native Disulfide Bond Formation in Proteins

Native disulfide bond formation is essential for the folding of many proteins. The enzyme protein disulfide isomerase (POI) catalyzes native disulfide bond formation using a Cys-Gly-HisCys active site. The active-site properties of POI (thiol pK. = 6.7 and disulfide E;O' = -180 mY) are critical for efficient catalysis. This Dissertation describes the design, synthesis, and characterization of s...