Autocitrullination and Changes in the Activity of Peptidylarginine Deiminase 3 Induced by High Ca Concentrations.

Peptidylarginine deiminases (PADs) are enzymes that catalyze the Ca-dependent conversion of arginine residues into proteins to citrulline residues. Five PAD isozymes have been identified in mammals. Several studies have shown that the active-site pockets of these isozymes are formed when Ca ions are properly bound.

Structures of human peptidylarginine deiminase type III provide insights into substrate recognition and inhibitor design.

Peptidylarginine deiminase type III (PAD3) is an isozyme belonging to the PAD enzyme family that converts arginine to citrulline residue(s) within proteins. PAD3 is expressed in most differentiated keratinocytes of the epidermis and hair follicles, while S100A3, trichohyalin, and filaggrin are its principal substrates. In this study, the X-ray crystal structures of PAD3 in six states, including its complex with the PAD inhibitor Cl-amidine, were determined.

Optimal Mutant Model of Human S100A3 Protein Citrullinated at Arg51 by Peptidylarginine Deiminase Type III and Its Solution Structural Properties.

S100A3 protein, a member of the EF-hand-type Ca-binding S100 protein family, undergoes a Ca-/Zn-induced structural change to a tetrameric state upon specific citrullination of R51 in human hair cuticular cells. To elucidate the underlying mechanism, we prepared recombinant mutant S100A3 proteins, including R51A, R51C, R51E, R51K, and R51Q, as potential models of post-translationally modified S100A3 and evaluated their biophysical and biochemical properties relative to wild-type (WT) S100A3 and WT citrullinated in vitro. Size exclusion chromatography (SEC) showed that R51Q formed a tetramer in the presence of Ca, while Ca titration monitored by Trp fluorescence indicated that R51Q had Ca-binding properties similar to those of citrullinated S1003A.

Structure determination of the human TRPV1 ankyrin-repeat domain under nonreducing conditions.

TRPV1, a member of the transient receptor potential (TRP) channels family, has been found to be involved in redox sensing. The crystal structure of the human TRPV1 ankyrin-repeat domain (TRPV1-ARD) was determined at 4.5 Å resolution under nonreducing conditions.