Structure Report for: 5OLJ

Dean Rea, Roos Van Elzen, Hans De Winter, Sebastiaan Van Goethem, Bart Landuyt, Walter Luyten, Liliane Schoofs, Pieter Van Der Veken, Koen Augustyns, Ingrid De Meester, Vilmos Flop, Anne-Marie Lambeir

Title: Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling
Rea D, Van Elzen R, De Winter H, Van Goethem S, Landuyt B, Luyten W, Schoofs L, Van der Veken P, Augustyns K and Lambeir AM <2 more 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 (- 2)
Ref: Eur Journal of Medicinal Chemistry, 139:482, 2017 : PubMed
Abstract


ESTHER: Rea_2017_Eur.J.Med.Chem_139_482
PubMedSearch: Rea 2017 Eur.J.Med.Chem 139 482
PubMedID: 28826083
Gene_locus related to this paper: porgi-DPP

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.