Peptidylarginine deiminase type 1 (PAD1)

Peptidylarginine deiminase type 1 (PAD1) is a calcium-dependent enzyme that catalyzes the conversion of arginine residues in proteins to citrulline, a process known as deimination or citrullination. This post-translational modification alters protein structure and function. PAD1 exhibits distinct tissue distribution, with highest expression in the epidermis where it is essential for late-stage epidermal differentiation, maintenance of skin barrier function, and cornification (keratinocyte terminal differentiation and programmed cell death). PAD1 deiminates proteins such as filaggrin and keratin K1, which is critical for normal skin hydration and barrier integrity. PAD1 deficiency impairs protein deimination in reconstructed human epidermis, leading to defective barrier function, abnormal keratinocyte differentiation, and altered epidermal homeostasis. PAD1 is one of the five human PAD isozymes (PAD1–PAD4, PAD6), each with their own substrate specificity and tissue distribution. The structure of active human PAD1 has been resolved at 3.2 Å in the presence of calcium. Inhibition of PAD enzymes is a subject of drug development, but selective PAD1 inhibitors are not yet available.

Other names

PADI1PAD IProtein-arginine deiminase type-1

Irreversible cysteine hydrogen bond formation at active site; small molecules inhibit calcium-dependent catalysis of arginine deimination.