Rea_2017_Eur.J.Med.Chem_139_482

Reference

Title : Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling - Rea_2017_Eur.J.Med.Chem_139_482
Author(s) : Rea D , Van Elzen R , De Winter H , Van Goethem S , Landuyt B , Luyten W , Schoofs L , Van der Veken P , Augustyns K , De Meester I , Fulop V , Lambeir AM
Ref : Eur Journal of Medicinal Chemistry , 139 :482 , 2017
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 A 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.

PubMedSearch : Rea_2017_Eur.J.Med.Chem_139_482
PubMedID: 28826083
Gene_locus related to this paper: porgi-DPP

Related information

Gene_locus porgi-DPP
Family porgi-DPP    DPP4N_Peptidase_S9
Structure porgi-DPP    DPP4N_Peptidase_S9    5OLJ

Citations formats

Rea D, Van Elzen R, De Winter H, Van Goethem S, Landuyt B, Luyten W, Schoofs L, Van der Veken P, Augustyns K, De Meester I, Fulop V, Lambeir AM (2017)
Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling
Eur Journal of Medicinal Chemistry 139 :482

Rea D, Van Elzen R, De Winter H, Van Goethem S, Landuyt B, Luyten W, Schoofs L, Van der Veken P, Augustyns K, De Meester I, Fulop V, Lambeir AM (2017)
Eur Journal of Medicinal Chemistry 139 :482