5OLJ

Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4

Summary for 5OLJ

• Entry DOI: 10.2210/pdb5olj/pdb
• Descriptor: Dipeptidyl peptidase IV, GLYCEROL (3 entities in total)
• Functional Keywords: dipeptidyl peptidase 4, peptidase inhibitor, porphyromonas gingivalis, biofilm, dipeptidyl peptidase 9, hydrolase
• Biological source: Porphyromonas gingivalis
• Total number of polymer chains: 1
• Total formula weight: 82179.81

Authors

Fulop, V. (deposition date: 2017-07-27, release date: 2017-09-06, Last modification date: 2024-01-17)

Primary citation

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, A.M.
Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling.
Eur J Med Chem, 139:482-491, 2017

PubMed 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.

PubMed: 28826083
DOI: 10.1016/j.ejmech.2017.08.024

Experimental method

X-RAY DIFFRACTION (2.2 Å)