2DW5

Crystal structure of human peptidylarginine deiminase 4 in complex with N-alpha-benzoyl-N5-(2-fluoro-1-iminoethyl)-L-ornithine amide

Summary for 2DW5

• Entry DOI: 10.2210/pdb2dw5/pdb
• Related: 1WD8 1WD9 1WDA 2DEW 2DEX 2DEY
• Descriptor: Protein-arginine deiminase type-4, CALCIUM ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: protein-inhibitor complex, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9UM07
• Total number of polymer chains: 1
• Total formula weight: 75730.81

Authors

Luo, Y.,Arita, K.,Sato, M.,Thompson, P.R. (deposition date: 2006-08-04, release date: 2006-10-17, Last modification date: 2024-11-20)

Primary citation

Luo, Y.,Arita, K.,Bhatia, M.,Knuckley, B.,Lee, Y.H.,Stallcup, M.R.,Sato, M.,Thompson, P.R.
Inhibitors and Inactivators of Protein Arginine Deiminase 4: Functional and Structural Characterization
Biochemistry, 45:11727-11736, 2006

PubMed Abstract: Protein arginine deiminase 4 (PAD4) is a transcriptional coregulator that catalyzes the calcium-dependent conversion of specific arginine residues in proteins to citrulline. Recently, we reported the synthesis and characterization of F-amidine, a potent and bioavailable irreversible inactivator of PAD4. Herein, we report our efforts to identify the steric and leaving group requirements for F-amidine-induced PAD4 inactivation, the structure of the PAD4-F-amidine x calcium complex, and in vivo studies with N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine), a PAD4 inactivator with enhanced potency. The PAD4 inactivators described herein will be useful pharmacological probes in characterizing the incompletely defined physiological role(s) of this enzyme. In addition, they represent potential lead compounds for the treatment of rheumatoid arthritis because a growing body of evidence supports a role for PAD4 in the onset and progression of this chronic autoimmune disorder.

PubMed: 17002273
DOI: 10.1021/bi061180d

Experimental method

X-RAY DIFFRACTION (2.3 Å)