U.S. Department of Health and Human Services

Biological Chemistry: How Is a Rare Bond Created?

An ancient enzyme that can be traced back 500 million years forms the chemical “rivet” that reinforces connective tissue throughout the body. This “sulfilimine” chemical bond links a nitrogen and sulfur atom in a manner that had not been observed in a biological system until 3 years ago. The sulfilimine bond reinforces the collagen IV network, which in the kidney, provides the structural scaffolding for the glomerular basement membrane. Researchers explored the chemistry underlying the creation of this rare bond and found that it is created by the enzyme peroxidasin. 

The researchers used cultured mouse cells to study the how the sulfilimine bond that links one collagen segment to another is created. They characterized each of the components and steps involved in the formation of this bond by peroxidasin, which include the generation of a highly reactive and potentially toxic intermediate acid that is similar to household bleach. The elucidation of the process that leads to the creation of this rare chemical bond is an important advance in researchers’ knowledge of collagen biochemistry at a fundamental level and provides broader insights into one way that these networks are stabilized. 

Levels of peroxidasin are increased in models of high blood pressure and atherosclerosis, suggesting that it may play a role in inflammation and disease. The researchers hypothesize that these findings could also provide insight into treatment of the autoimmune disease Goodpasture’s syndrome, in which antibodies target collagen IV molecules. Future studies may elucidate additional roles of this enzyme in a variety of diseases and illuminate possible approaches to treatment. 

Bhave G, Cummings CF, Vanacore RM, et al. Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis. Nat Chem Biol 8: 784-790, 2012