PXD009950

PXD009950 is an original dataset announced via ProteomeXchange.

Title	Gingipain transpeptidation
Description	Porphyromonas gingivalis is a keystone periodontal pathogen that has been associated with autoimmune disorders. The cell surface proteases Lys-gingipain (Kgp) and Arg-gingipains (RgpA and RgpB) are major virulence factors and their proteolytic activity is enhanced by small peptides such as glycylglycine (GlyGly). The reaction kinetics suggested that GlyGly may function as an acceptor molecule for gingipain-catalysed transpeptidation. Purified gingipains and P. gingivalis whole cells were used to digest selected substrates including human haemoglobin in the presence or absence of peptide acceptors. Mass spectrometric analysis of the substrates digested with gingipains in the presence of GlyGly showed that transpeptidation outcompeted hydrolysis while the trypsin-digested controls exhibited predominantly hydrolysis activity. The transpeptidation levels increased with increasing concentration of GlyGly. Purified gingipains and whole cells exhibited extensive transpeptidation activities on human haemoglobin. All haemoglobin cleavage sites were found to be suitable for GlyGly transpeptidation and this transpeptidation enhanced haemoglobin digestion. The transpeptidation products were often more abundant than the corresponding hydrolysis products. In the absence of GlyGly, haemoglobin peptides produced during digestion were utilised as acceptors leading to the detection of up to 116 different transpeptidation products in a single reaction. P. gingivalis cells were able to digest haemoglobin faster when acceptor peptides derived from human serum albumin were included in the reaction suggesting that gingipain-catalysed transpeptidation may be relevant for substrates encountered in vivo. The transpeptidation of host proteins in vivo may potentially lead to the breakdown of immunological tolerance culminating in autoimmune reactions.
HostingRepository	PRIDE
AnnounceDate	2018-07-11
AnnouncementXML	Submission_2018-07-11_07:20:00.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009950
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Paul Veith
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl; Oxidation; Cysteinyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-29 02:30:44	ID requested
⏵ 1	2018-07-11 07:20:02	announced

Zhang L, Veith PD, Huq NL, Chen YY, Seers CA, Cross KJ, Gorasia DG, Reynolds EC, Porphyromonas gingivalis Gingipains Display Transpeptidation Activity. J Proteome Res, 17(8):2803-2818(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: gingipains, transpeptidation, hemoglobin, porphyromonas gingivalis

Eric Charles Reynolds
contact affiliation	Melbourne Dental School, University of Melbourne, Australia
contact email	e.reynolds@unimelb.edu.au
lab head
Paul Veith
contact affiliation	Melbourne Dental School
contact email	pdv@unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009950
     1. Label: PRIDE project
     2. Name: Gingipain transpeptidation