1WD9

Calcium bound form of human peptidylarginine deiminase type4 (PAD4)

Summary for 1WD9

• Entry DOI: 10.2210/pdb1wd9/pdb
• Related: 1WD8 1WDA
• Descriptor: Protein-arginine deiminase type IV, CALCIUM ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: post-translational enzyme, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9UM07
• Total number of polymer chains: 1
• Total formula weight: 75274.26

Authors

Arita, K.,Hashimoto, H.,Shimizu, T.,Nakashima, K.,Yamada, M.,Sato, M. (deposition date: 2004-05-12, release date: 2004-07-13, Last modification date: 2024-05-29)

Primary citation

Arita, K.,Hashimoto, H.,Shimizu, T.,Nakashima, K.,Yamada, M.,Sato, M.
Structural basis for Ca(2+)-induced activation of human PAD4
Nat.Struct.Mol.Biol., 11:777-783, 2004

PubMed Abstract: Peptidylarginine deiminase 4 (PAD4) is a Ca(2+)-dependent enzyme that catalyzes the conversion of protein arginine residues to citrulline. Its gene is a susceptibility locus for rheumatoid arthritis. Here we present the crystal structure of Ca(2+)-free wild-type PAD4, which shows that the polypeptide chain adopts an elongated fold in which the N-terminal domain forms two immunoglobulin-like subdomains, and the C-terminal domain forms an alpha/beta propeller structure. Five Ca(2+)-binding sites, none of which adopt an EF-hand motif, were identified in the structure of a Ca(2+)-bound inactive mutant with and without bound substrate. These structural data indicate that Ca(2+) binding induces conformational changes that generate the active site cleft. Our findings identify a novel mechanism for enzyme activation by Ca(2+) ions, and are important for understanding the mechanism of protein citrullination and for developing PAD-inhibiting drugs for the treatment of rheumatoid arthritis.

PubMed: 15247907
DOI: 10.1038/nsmb799

Experimental method

X-RAY DIFFRACTION (2.6 Å)