4YTG: Crystal Structure Of Porphyromonas Gingivalis Peptidylarginine Deiminase (ppad) Mutant C351a In Complex With Dipeptide Met-arg

Citation:
Abstract
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.
PDB ID: 4YTGDownload
MMDB ID: 130558
PDB Deposition Date: 2015/3/17
Updated in MMDB: 2016/09
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4YTG: monomeric; determined by software (PISA)
Molecular Components in 4YTG
Label Count Molecule
Protein (1 molecule)
1
Peptidylarginine Deiminase(Gene symbol: PGN_RS04285)
Molecule annotation
Chemicals (11 molecules)
1
1
2
1
3
1
4
5
5
1
6
2
* Click molecule labels to explore molecular sequence information.

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