Peroxidasin in extracellular matrix remodeling: Structure, catalytic mechanisms, pathological roles, and pharmacological modulation.

Abstract

Peroxidasin (PXDN) is a multidomain extracellular heme peroxidase that uses hydrogen peroxide (H2O2) to oxidize bromide (Br-) to hypobromous acid (HOBr), thereby promoting sulfilimine bond formation between adjacent non-collagenous 1 (NC1) domains of collagen IV and maintaining basement membrane integrity. Beyond this canonical reaction, PXDN may regulate extracellular matrix (ECM) remodeling through broader oxidative or brominating modifications of extracellular proteins. Dysregulated PXDN expression or activity has been associated with pathological ECM remodeling in fibrosis, cancer, renal disease, vascular disorders, and other matrix-related conditions. This review discusses PXDN domain organization, heme-dependent catalysis, ECM-associated functions, pathological remodeling, and current pharmacological approaches to PXDN modulation. Published pharmacological data are considered alongside predicted ligand interactions within the PXDN heme pocket.

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