Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling

Tools
- Tools
+ Tools

Rea, Dean, Van Elzen, Roos, De Winter, Hans, Van Goethem, Sebastiaan, Landuyt, Bart, Luyten, Walter, Schoofs, Liliane, Van Der Veken, Pieter, Augustyns, Koen, De Meester, Ingrid, Fülöp, Vilmos and Lambeir, Anne-Marie (2017) Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling. European Journal of Medicinal Chemistry, 139 . pp. 482-491. doi:10.1016/j.ejmech.2017.08.024 ISSN 0223-5234.

[img]
Preview
PDF
WRAP-crystal-structure-Porphyromonas-gingivalis-dipeptidyl-Fulop-2017.pdf - Accepted Version - Requires a PDF viewer.

Download (1300Kb) | Preview
[img] PDF
WRAP-supplementary-material.pdf - Supplemental Material
Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer.

Download (1251Kb)
Official URL: http://dx.doi.org/10.1016/j.ejmech.2017.08.024

Request Changes to record.

Abstract

The Gram-negative anaerobe Porphyromonas gingivalis is associated with chronic periodontitis. Clinical isolates of P. gingivalis strains with high dipeptidyl peptidase 4 (DPP4) expression also had a high capacity for biofilm formation and were more infective. The X-ray crystal structure of P. gingivalis DPP4 was solved at 2.2 Å resolution. Despite a sequence identity of 32%, the overall structure of the dimer was conserved between P. gingivalis DPP4 and mammalian orthologues. The structures of the substrate binding sites were also conserved, except for the region called S2-extensive, which is exploited by specific human DPP4 inhibitors currently used as antidiabetic drugs. Screening of a collection of 450 compounds as inhibitors revealed a structure-activity relationship that mimics in part that of mammalian DPP9. The functional similarity between human and bacterial DPP4 was confirmed using 124 potential peptide substrates.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
R Medicine > RK Dentistry
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Porphyromonas gingivalis, Periodontal disease
Journal or Publication Title: European Journal of Medicinal Chemistry
Publisher: Elsevier Masson
ISSN: 0223-5234
Official Date: 20 October 2017
Dates:
DateEvent
20 October 2017Published
10 August 2017Available
8 August 2017Accepted
Volume: 139
Page Range: pp. 482-491
DOI: 10.1016/j.ejmech.2017.08.024
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Date of first compliant deposit: 1 November 2017
Date of first compliant Open Access: 10 August 2018
Funder: Fonds Wetenschappelijk Onderzoek (FWO), Agentschap voor Innovatie door Wetenschap en Technologie (Belgium) (IWT), Katholieke Universiteit te Leuven (1970- ), Seventh Framework Programme (European Commission) (FP7)
Grant number: Project code G.0173.09N (FWO), Grant SBO 50164, IOF/KP/09/003 (Katholieke Universiteit te Leuven (1970- )), EU-FP7 HEALTH-Proposal No. 223077 NEUROPRO (FP7)

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us