4ytb

Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) in complex with dipeptide Asp-Gln.

spinqualitylabelsall models 4ytb, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ytb is a 1 chain structure with sequence from Porphyromonas gingivalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ASP, AZI, CL, GLN, GOL, IMD, NA, PO4 Related: 4yt9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PAD_PORGI] Deiminates the guanidino group of C-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. May promote the growth of the pathogen in the periodontal pocket by producing ammonia, ammonia having a protective effect during acidic cleaning cycles in the mouth. Publication Abstract from PubMed Citrullination is a post-translational modification of higher organisms that deiminates arginines in proteins and peptides. It occurs in physiological processes but also pathologies such as multiple sclerosis, fibrosis, Alzheimer's disease and rheumatoid arthritis (RA). The reaction is catalyzed by peptidylarginine deiminases (PADs), which are found in vertebrates but not in lower organisms. RA has been epidemiologically associated with periodontal disease, whose main infective agent is Porphyromonas gingivalis. Uniquely among microbes, P. gingivalis secretes a PAD, termed PPAD (Porphyromonas peptidylarginine deiminase), which is genetically unrelated to eukaryotic PADs. Here, we studied function of PPAD and its substrate-free, substrate-complex, and substrate-mimic-complex structures. It comprises a flat cylindrical catalytic domain with five-fold alpha/beta-propeller architecture and a C-terminal immunoglobulin-like domain. The PPAD active site is a funnel located on one of the cylinder bases. It accommodates arginines from peptide substrates after major rearrangement of a "Michaelis loop" that closes the cleft. The guanidinium and carboxylate groups of substrates are tightly bound, which explains activity of PPAD against arginines at C-termini but not within peptides. Catalysis is based on a cysteine-histidine-asparagine triad, which is shared with human PAD1-PAD4 and other guanidino-group modifying enzymes. We provide a working mechanism hypothesis based on 18 structure-derived point mutants. Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase.,Goulas T, Mizgalska D, Garcia-Ferrer I, Kantyka T, Guevara T, Szmigielski B, Sroka A, Millan C, Uson I, Veillard F, Potempa B, Mydel P, Sola M, Potempa J, Gomis-Ruth FX Sci Rep. 2015 Jul 1;5:11969. doi: 10.1038/srep11969. PMID:26132828 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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