1wd8
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= | ||
| - | |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=[[1wd9|1WD9]], [[1wda|1WDA]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wd8 OCA], [http://www.ebi.ac.uk/pdbsum/1wd8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wd8 RCSB]</span> | ||
}} | }} | ||
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==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== | ||
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[[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 00:34:40 2008'' |
Revision as of 21:34, 30 March 2008
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| , resolution 2.80Å | |||||||
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| Activity: | Protein-arginine deiminase, with EC number 3.5.3.15 | ||||||
| Related: | 1WD9, 1WDA
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Calcium free 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
1WD8 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
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