Protein-arginine deiminase
| protein-arginine deiminase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Protein-arginine deiminase 4, dimer, Human | |||||||||
| Identifiers | |||||||||
| EC no. | 3.5.3.15 | ||||||||
| CAS no. | 75536-80-0 | ||||||||
| Databases | |||||||||
| BRENDA | enzyme data | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | enzyme entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| Rhea | reactions | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
In enzymology, a protein-arginine deiminase (PAD) (EC 3.5.3.15) is an enzyme that catalyzes a form of post translational modification called arginine de-imination or citrullination:
- protein L-arginine + H2O protein L-citrulline + NH3
Thus, the two substrates of this enzyme are protein L-arginine (arginine residue inside a protein) and H2O, whereas its two products are protein L-citrulline and NH3:
This enzyme belongs to the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in linear amidines. The systematic name of this enzyme class is protein-L-arginine iminohydrolase. This enzyme is also called peptidylarginine deiminase.
Structural studies
As of late 2007, seven structures have been solved for this class of enzymes, with PDB accession codes PDB: 1WD8, PDB: 1WD9, PDB: 1WDA, PDB: 2DEW, PDB: 2DEX, PDB: 2DEY, and PDB: 2DW5.
Mammalian proteins
Mammals have 5 protein-arginine deiminases, with symbols
except for rodents, there the letter case is different:
- Padi1, Padi2, Padi3, Padi4, Padi6[3]
The different case is just a historical artifact. It doesn't indicate that the rodent proteins are special.
Inhibitors
Irreversible inhibitors
- Cl-amidine, BB-Cl-Amidine,[4] YW3-56[5]
Reversible inhibitors
- GSK484, GSK199
References
- ↑ Sams, K.L; Mukai, C; Marks, B.A; Mittal, C; Demeter, E.A; Nelissen, S; Grenier, J.K; Tate, A.E; Ahmed, F; Coonrod, S.A (October 2022). "Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice". Reprod Biol Endocrinol. 20 (1): 150. doi:10.1186/s12958-022-01018-w. PMC 9555066. PMID 36224627.
- ↑ "Search results for "peptidyl arginine deiminase"". Vertebrate Gene Nomenclature Committee. Retrieved 9 February 2022.
- ↑ "Protein Superfamily Detail: Protein-arginine_deiminase". Mouse Genome Informatics.
- ↑ Mondal, S.; Thompson, P.R. (2019). "Protein Arginine Deiminases (PADs): Biochemistry and Chemical Biology of Protein Citrullination". Acc. Chem. Res. 52 (3): 818–832. doi:10.1021/acs.accounts.9b00024. PMC 6443095. PMID 30844238.
- ↑ Wang, Y; Li, P.; Wang, S. (2012). "Anticancer Peptidylarginine Deiminase (PAD) Inhibitors Regulate the Autophagy Flux and the Mammalian Target of Rapamycin Complex 1 Activity". J. Biol. Chem. 287 (31): 818–832. doi:10.1074/jbc.M112.375725. PMC 3406678. PMID 22605338.
- Fujisaki M, Sugawara K (January 1981). "Properties of peptidylarginine deiminase from the epidermis of newborn rats". J. Biochem. 89 (1). Tokyo: 257–63. doi:10.1093/oxfordjournals.jbchem.a133189. PMID 7217033.
- protein-arginine+deiminase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)