S46 peptidases are the first exopeptidases to be members of clan PA.
The dipeptidyl aminopeptidase BII (DAP BII) belongs to a serine peptidase family, S46. The amino acid sequence of the catalytic unit of DAP BII exhibits significant similarity to those of clan PA endopeptidases, such as chymotrypsin. However, the molecular mechanism of the exopeptidase activity of family S46 peptidase is unknown. Here, we report crystal structures of DAP BII. DAP BII contains a peptidase domain including a typical double β-barrel fold and previously unreported α-helical domain. The structures of peptide complexes revealed that the α-helical domain covers the active-site cleft and the side chain of Asn330 in the domain forms hydrogen bonds with the N-terminus of the bound peptide. These observations indicate that the α-helical domain regulates the exopeptidase activity of DAP BII. Because S46 peptidases are not found in mammals, we expect that our study will be useful for the design of specific inhibitors of S46 peptidases from pathogens.
1] School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, JAPAN [2].
Yasumitsu
Y
Sakamoto
1] Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, JAPAN [2].
Yoshiyuki
Y
Suzuki
School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, JAPAN.
Ippei
I
Iizuka
School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, JAPAN.
Chika
C
Tateoka
School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, JAPAN.
Saori
S
Roppongi
School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, JAPAN.
Mayu
M
Fujimoto
Maruwa Foods and Biosciences Inc., 170-1 Tsutsui-cho, Yamatokoriyama, Nara 639-1123, Japan.
Koji
K
Inaka
Confocal Science Inc., 2-12-2 Iwamoto-cho, Chiyoda-ku, Tokyo 101-0032, Japan.
Hiroaki
H
Tanaka
Japan Aerospace Exploration Agency, 2-1-1 Sengen, Tsukuba, Ibaraki 305-8505, Japan.
Mika
M
Masaki
Japan Aerospace Exploration Agency, 2-1-1 Sengen, Tsukuba, Ibaraki 305-8505, Japan.
Kazunori
K
Ohta
Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, JAPAN.
Hirofumi
H
Okada
School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, JAPAN.
Takamasa
T
Nonaka
Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, JAPAN.
Yasushi
Y
Morikawa
School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, JAPAN.
Kazuo T
KT
Nakamura
Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, JAPAN.
Wataru
W
Ogasawara
School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, JAPAN.
Nobutada
N
Tanaka
D000595:Amino Acid Sequence; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray / Q000379:methods; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry*; D020689:Exopeptidases / Q000737:chemistry*; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D020689:Exopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C059010:dipeptidyl aminopeptidase B