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1wd8
From Proteopedia
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(New page: 200px<br /> <applet load="1wd8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wd8, resolution 2.80Å" /> '''Calcium free form o...)
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Revision as of 17:42, 12 November 2007
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Calcium free form of human peptidylarginine deiminase type4 (PAD4)
Contents |
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.
Disease
Known diseases associated with this structure: Rheumatoid arthritis, susceptibility to OMIM:[605347]
About this Structure
1WD8 is a Single protein structure of sequence from Homo sapiens. Active as Protein-arginine deiminase, with EC number 3.5.3.15 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 Nov 12 19:49:19 2007
