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5ak8

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Revision as of 06:13, 20 June 2018

Structure of C351A mutant of Porphyromonas gingivalis peptidylarginine deiminase

Structural highlights

5ak8 is a 1 chain structure with sequence from Atcc 33277. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	5ak7
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.^[1]

Publication Abstract from PubMed

BACKGROUND: Periodontitis (PD) is a known risk factor for rheumatoid arthritis (RA) and there is increasing evidence that the link between the two diseases is due to citrullination by the unique bacterial peptidylarginine deiminase (PAD) enzyme expressed by periodontal pathogen Pophyromonas gingivalis (PPAD). However, the precise mechanism by which PPAD could generate potentially immunogenic peptides has remained controversial due to lack of information about the structural and catalytic mechanisms of the enzyme. OBJECTIVES: By solving the 3D structure of PPAD we aim to characterise activity and elucidate potential mechanisms involved in breach of tolerance to citrullinated proteins in RA. METHODS: PPAD and a catalytically inactive mutant PPADC351A were crystallised and their 3D structures solved. Key residues identified from 3D structures were examined by mutations. Fibrinogen and alpha-enolase were incubated with PPAD and P. gingivalis arginine gingipain (RgpB) and citrullinated peptides formed were sequenced and quantified by mass spectrometry. RESULTS: Here, we solve the crystal structure of a truncated, highly active form of PPAD. We confirm catalysis is mediated by the following residues: Asp130, His236, Asp238, Asn297 and Cys351 and show Arg152 and Arg154 may determine the substrate specificity of PPAD for C-terminal arginines. We demonstrate the formation of 37 C-terminally citrullinated peptides from fibrinogen and 11 from alpha-enolase following incubation with tPPAD and RgpB. CONCLUSIONS: PPAD displays an unequivocal specificity for C-terminal arginine residues and readily citrullinates peptides from key RA autoantigens. The formation of these novel citrullinated peptides may be involved in breach of tolerance to citrullinated proteins in RA.

Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis.,Montgomery AB, Kopec J, Shrestha L, Thezenas ML, Burgess-Brown NA, Fischer R, Yue WW, Venables PJ Ann Rheum Dis. 2015 Jul 24. pii: annrheumdis-2015-207656. doi:, 10.1136/annrheumdis-2015-207656. PMID:26209657^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McGraw WT, Potempa J, Farley D, Travis J. Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect Immun. 1999 Jul;67(7):3248-56. PMID:10377098
↑ Montgomery AB, Kopec J, Shrestha L, Thezenas ML, Burgess-Brown NA, Fischer R, Yue WW, Venables PJ. Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis. Ann Rheum Dis. 2015 Jul 24. pii: annrheumdis-2015-207656. doi:, 10.1136/annrheumdis-2015-207656. PMID:26209657 doi:http://dx.doi.org/10.1136/annrheumdis-2015-207656

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ak8"

@@ Line 3: / Line 3: @@
 <StructureSection load='5ak8' size='340' side='right' caption='[[5ak8]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ak8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AK8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AK8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ak8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33277 Atcc 33277]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AK8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AK8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ak7|5ak7]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ak8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ak8 OCA], [http://pdbe.org/5ak8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ak8 RCSB], [http://www.ebi.ac.uk/pdbsum/5ak8 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ak8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ak8 OCA], [http://pdbe.org/5ak8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ak8 RCSB], [http://www.ebi.ac.uk/pdbsum/5ak8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ak8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Atcc 33277]]
 [[Category: Burgess-Brown, N]]
 [[Category: Kiyani, W]]

5ak8

From Proteopedia

Revision as of 06:13, 20 June 2018

Structure of C351A mutant of Porphyromonas gingivalis peptidylarginine deiminase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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