title: Structural and mutational analyses of dipeptidyl peptidase 11 from Porphyromonas gingivalis reveal the molecular basis for strict substrate specificity.
abstract: The dipeptidyl peptidase 11 from Porphyromonas gingivalis (PgDPP11) belongs to the S46 family of serine peptidases and preferentially cleaves substrates with Asp/Glu at the P1 position. The molecular mechanism underlying the substrate specificity of PgDPP11, however, is unknown. Here, we report the crystal structure of PgDPP11. The enzyme contains a catalytic domain with a typical double β-barrel fold and a recently identified regulatory α-helical domain. Crystal structure analyses, docking studies, and biochemical studies revealed that the side chain of Arg673 in the S1 subsite is essential for recognition of the Asp/Glu side chain at the P1 position of the bound substrate. Because S46 peptidases are not found in mammals and the Arg673 is conserved among DPP11s, we anticipate that DPP11s could be utilised as targets for antibiotics. In addition, the present structure analyses could be useful templates for the design of specific inhibitors of DPP11s from pathogenic organisms.
authors.affiliation: School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan.
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Iizuka
authors.affiliation: School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Tateoka
authors.affiliation: School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Roppongi
authors.affiliation: School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Maruwa Foods and Biosciences Inc., 170-1 Tsutsui-cho, Yamatokoriyama, Nara 639-1123, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Inaka
authors.affiliation: Confocal Science Inc., 2-12-2 Iwamoto-cho, Chiyoda-ku, Tokyo 101-0032, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Japan Aerospace Exploration Agency, 2-1-1 Sengen, Tsukuba, Ibaraki 305-8505, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Japan Aerospace Exploration Agency, 2-1-1 Sengen, Tsukuba, Ibaraki 305-8505, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohta
authors.affiliation: School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Gouda
authors.affiliation: School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogasawara
authors.affiliation: School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Nobutada
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II