September 9, 2015

How to build a basement

Understanding the action of a certain enzyme will shed light on basement membrane function, and on disorders ranging from diabetic kidney disease to cancer.

by Sanjay Mishra

The evolutionarily conserved enzyme peroxidasin forms the sulfilimine bond, which reinforces the collagen IV scaffold found in connective tissue throughout the body. Both are essential for the integrity and tissue development of basement membranes.

Now in a study published in the Journal of Biological Chemistry, Isi Ero-Tolliver, Ph.D., Billy G. Hudson, Ph.D., and Gautam (Jay) Bhave, M.D., Ph.D., show that among animal peroxidases, only peroxidasin efficiently cross-links collagen IV.

They also demonstrate that both the catalytic and non-catalytic immunoglobulin domains of the enzyme are uniquely required for the sulfilimine bond formation. This distinguishes peroxidasin from other peroxidases.

The Hudson lab first reported the novel sulfur-nitrogen bond in 2009 and, subsequently, the role of peroxidasin in forming it. In 2014, the researchers demonstrated that the enzyme critically and uniquely needs bromine as an essential “co-factor.”

Understanding how the enzyme cross-links collagen IV will shed light on basement membrane function, and on disorders ranging from diabetic kidney disease to cancer, they said.

The study was supported in part by National Institutes of Health grants DK018381 and DK097306.

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