Structural insight into the function of human peptidyl arginine deiminase 6.

ABSTRACT: Peptidyl arginine deiminase 6 (PADI6 or PAD6) is vital for early embryonic development in mice and humans, yet its function remains elusive. PADI6 is less conserved than other PADIs and it is currently unknown whether it has a catalytic function. Here we show that human PADI6 dimerises like hPADIs 2-4, however, does not bind Ca²⁺ and is inactive in in vitro assays against standard PADI substrates. By determining the crystal structure of hPADI6, we show that hPADI6 is structured in the absence of Ca²⁺ where hPADI2 and hPADI4 are not, and the Ca-binding sites are not conserved. Moreover, we show that whilst the key catalytic aspartic acid and histidine residues are structurally conserved, the cysteine is displaced far from the active site centre and the hPADI6 ac

SUBMITTER: Williams JPC 

PROVIDER: S-EPMC11402830 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature