A novel Porphyromonas gingivalis enzyme: An atypical dipeptidyl peptidase III with an ARM repeat domain

• DOI: 10.1371/journal.pone.0188915
• Publication Date: 2017-11-30T23:16:26Z
• Authors: Altijana Hromić-J...; Nina Jajčanin Jozić; Saša Kazazić; Marina Grabar Bra...; Zrinka Karačić; Jörg H. Schrittwi...; Krishna Mohan Pad...; Marko Tomin; Monika Oberer; Karl Gruber; Marija Abramić; Sanja Tomić
• Keywords: Bacteroides thetaiotaomicron

Porphyromonas gingivalis, an asaccharolytic Gram-negative oral anaerobe, is a major pathogen associated with adult periodontitis, chronic infective disease that significant percentage of the human population suffers from. It preferentially utilizes dipeptides as its carbon source, suggesting importance dipeptidyl peptidase (DPP) types enzyme for growth. Until now DPP IV, DPP5, 7 and 11 have been extensively investigated. Here, we report characterization III using molecular biology, biochemical, biophysical computational chemistry methods. In addition to expected evolutionarily conserved regions all family members, PgDPP possesses C-terminal extension containing Armadillo (ARM) type fold similar AlkD bacterial DNA glycosylases, implicating it in alkylation repair functions. However, complementation assays repair-deficient Escherichia coli strain indicated absence function III. Biochemical analyses recombinant revealed activity from Bacteroides thetaiotaomicron, range between activities yeast counterparts. catalytic efficiency separately expressed domain ~1000-fold weaker. The structure dynamics ligand-free complex two different diarginyl arylamide substrates was investigated small angle X-ray scattering, homology modeling, MD simulations hydrogen/deuterium exchange (HDX). correlation experimental HDX data improved simulation time, adopts semi-closed or closed form solution, reported obtained results reveal atypical increased structural complexity: superhelical contributes influences interdomain dynamics. Overall, this research reveals multifunctionality opens direction future proteins.