1wd9
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1wd9 |SIZE=350|CAPTION= <scene name='initialview01'>1wd9</scene>, resolution 2.60Å | |PDB= 1wd9 |SIZE=350|CAPTION= <scene name='initialview01'>1wd9</scene>, resolution 2.60Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1wd8|1WD8]], [[1wda|1WDA]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wd9 OCA], [http://www.ebi.ac.uk/pdbsum/1wd9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wd9 RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Rheumatoid arthritis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605347 605347]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 32: | Line 32: | ||
[[Category: Shimizu, T.]] | [[Category: Shimizu, T.]] | ||
[[Category: Yamada, M.]] | [[Category: Yamada, M.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: SO4]] | ||
[[Category: post-translational enzyme]] | [[Category: post-translational enzyme]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:34:45 2008'' |
Revision as of 21:34, 30 March 2008
| |||||||
| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Protein-arginine deiminase, with EC number 3.5.3.15 | ||||||
| Related: | 1WD8, 1WDA
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Calcium bound form of human peptidylarginine deiminase type4 (PAD4)
Overview
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.
About this Structure
1WD9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for Ca(2+)-induced activation of human PAD4., Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M, Nat Struct Mol Biol. 2004 Aug;11(8):777-83. Epub 2004 Jul 11. PMID:15247907
Page seeded by OCA on Mon Mar 31 00:34:45 2008
