title: Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis.
abstract: Collagen IV comprises the predominant protein network of basement membranes, a specialized extracellular matrix, which underlie epithelia and endothelia. These networks assemble through oligomerization and covalent crosslinking to endow mechanical strength and shape cell behavior through interactions with cell-surface receptors. A recently discovered sulfilimine (S=N) bond between a methionine sulfur and hydroxylysine nitrogen reinforces the collagen IV network. We demonstrate that peroxidasin, an enzyme found in basement membranes, catalyzes formation of the sulfilimine bond. Drosophila peroxidasin mutants have disorganized collagen IV networks and torn visceral muscle basement membranes, pointing to a critical role for the enzyme in tissue biogenesis. Peroxidasin generates hypohalous acids as reaction intermediates, suggesting a paradoxically anabolic role for these usually destructive oxidants. This work highlights sulfilimine bond formation as what is to our knowledge the first known physiologic function for peroxidasin, a role for hypohalous oxidants in tissue biogenesis, and a possible role for peroxidasin in inflammatory diseases.
authors: Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Gautam
authors: G
authors: Bhave
authors: Christopher F
authors: CF
authors: Cummings
authors: Roberto M
authors: RM
authors: Vanacore
authors: Chino
authors: C
authors: Kumagai-Cresse
authors: Isi A
authors: IA
authors: Ero-Tolliver
authors: Mohamed
authors: M
authors: Rafi
authors: Jeong-Suk
authors: JS
authors: Kang
authors: Vadim
authors: V
authors: Pedchenko
authors: Liselotte I
authors: LI
authors: Fessler
authors: John H
authors: JH
authors: Fessler
authors: Billy G
authors: BG
authors: Hudson
mesh_terms: D000143:Acids / Q000737:chemistry*; D000818:Animals; D002384:Catalysis; D024141:Collagen Type IV / Q000737:chemistry; D004330:Drosophila / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D009195:Peroxidase / Q000737:chemistry*; D000097423:Peroxidasin
chemical_list: D000143:Acids; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D007097:Imines; D009195:Peroxidase; D000097423:Peroxidasin