7DAN

Structure of the Ca2+-bound wild-type peptidylarginine deiminase type III (PAD3)

Summary for 7DAN

• Entry DOI: 10.2210/pdb7dan/pdb
• Related: 7D4Y 7D56 7D5R 7D5V 7D8N
• Descriptor: Protein-arginine deiminase type-3, CALCIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: peptidylarginie deiminase, citrullination, post-translational modification, enzyme, active form, calcium, isozyme, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 226403.43

Authors

Sawata, M.,Unno, M. (deposition date: 2020-10-16, release date: 2021-06-02, Last modification date: 2023-11-29)

Primary citation

Funabashi, K.,Sawata, M.,Nagai, A.,Akimoto, M.,Mashimo, R.,Takahara, H.,Kizawa, K.,Thompson, P.R.,Ite, K.,Kitanishi, K.,Unno, M.
Structures of human peptidylarginine deiminase type III provide insights into substrate recognition and inhibitor design.
Arch.Biochem.Biophys., 708:108911-108911, 2021

PubMed Abstract: 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. This structural analysis identified a large space around Gly374 in the PAD3-Ca-Cl-amidine complex, which may be used to develop novel PAD3-selective inhibitors. In addition, similarities between PAD3 and PAD4 were found based on the investigation of PAD4 reactivity with S100A3 in vitro. A comparison of the structures of PAD1, PAD2, PAD3, and PAD4 implied that the flexibility of the structures around the active site may lead to different substrate selectivity among these PAD isozymes.

PubMed: 33971157
DOI: 10.1016/j.abb.2021.108911

Experimental method

X-RAY DIFFRACTION (3.1 Å)