Inaka K

References (4)

Title : Crystal structures of human dipeptidyl peptidase IV in its apo and diprotin B-complexed forms - Hiramatsu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_335
Author(s) : Hiramatsu H , Kyono K , Yamamoto A , Saeki K , Shima H , Sugiyama S , Inaka K , Shimizu R
Ref : Acta Biochim Biophys Sin (Shanghai) , 39 :335 , 2007
Abstract : Dipeptidyl peptidase IV (DPPIV), which belongs to the prolyl oligopeptidase family of serine proteases, is known to have a variety of regulatory biological functions and has been shown to be implicated in type 2 diabetes. It is therefore important to develop selective human DPPIV (hDPPIV) inhibitors. In this study, we determined the crystal structure of apo hDPPIV at 1.9 A resolution. Our high-resolution crystal structure of apo hDPPIV revealed the presence of sodium ion and glycerol molecules at the active site. In order to elucidate the hDPPIV binding mode and substrate specificity, we determined the crystal structure of hDPPIV-diprotin B (Val-Pro-Leu) complex at 2.1 A resolution, and clarified the difference in binding mode between diprotin B and diprotin A (Ile-Pro-Ile) into the active site of hDPPIV. Comparison between our crystal structures and the reported apo hDPPIV structures revealed that positively charged functional groups and conserved water molecules contributed to the interaction of ligands with hDPPIV. These results are useful for the design of potent hDPPIV inhibitors.
ESTHER : Hiramatsu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_335
PubMedSearch : Hiramatsu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_335
PubMedID: 17492130
Gene_locus related to this paper: human-DPP4

Title : The crystal structure of human dipeptidyl peptidase IV (DPPIV) complex with diprotin A - Hiramatsu_2004_Biol.Chem_385_561
Author(s) : Hiramatsu H , Yamamoto A , Kyono K , Higashiyama Y , Fukushima C , Shima H , Sugiyama S , Inaka K , Shimizu R
Ref : Biol Chem , 385 :561 , 2004
Abstract : Dipeptidyl peptidase IV (DPPIV) is a serine protease, a member of the prolyl oligopeptidase (POP) family, and has been implicated in several diseases. Therefore, it seems important to develop selective inhibitors for human DPPIV (hDPPIV) that are able to control the biological function of hDPPIV. In order to elucidate the binding mode and substrate specificity, we determined the crystal structure complex of hDPPIV and diprotin A (IIe-Pro-IIe), a slowly hydrolyzed substrate of hDPPIV, at 2.2 A resolution. In this paper, we discuss the molecular interaction mechanism of diprotin A with hDPPIV based on the X-ray crystal structure.
ESTHER : Hiramatsu_2004_Biol.Chem_385_561
PubMedSearch : Hiramatsu_2004_Biol.Chem_385_561
PubMedID: 15255191
Gene_locus related to this paper: human-DPP4

Title : The structure and function of human dipeptidyl peptidase IV, possessing a unique eight-bladed beta-propeller fold - Hiramatsu_2003_Biochem.Biophys.Res.Commun_302_849
Author(s) : Hiramatsu H , Kyono K , Higashiyama Y , Fukushima C , Shima H , Sugiyama S , Inaka K , Yamamoto A , Shimizu R
Ref : Biochemical & Biophysical Research Communications , 302 :849 , 2003
Abstract : Dipeptidyl peptidase IV (DPPIV) is a serine protease, a member of the prolyl oligopeptidase (POP) family, and has been implicated in several diseases. Therefore, the development of DPPIV selective inhibitors, which are able to control the biological function of DPPIV, is important. We determined the crystal structure of human DPPIV at 2.6A resolution. The molecule consists of a unique eight-bladed beta-propeller domain in the N-terminal region and a serine protease domain in the C-terminal region. Also, the large "cave" structure, which is thought to control the access of the substrate, is found on the side of the beta-propeller fold. Comparison of the overall amino acid sequence between human DPPIV and POP shows low homology (12.9%). In this paper, we report the structure of human DPPIV, especially focusing on a unique eight-bladed beta-propeller domain. We also discuss the way for the access of the substrate to this domain.
ESTHER : Hiramatsu_2003_Biochem.Biophys.Res.Commun_302_849
PubMedSearch : Hiramatsu_2003_Biochem.Biophys.Res.Commun_302_849
PubMedID: 12646248
Gene_locus related to this paper: human-DPP4

Title : Crystallization and preliminary X-ray study of human dipeptidyl peptidase IV (DPPIV) - Hiramatsu_2003_Acta.Crystallogr.D.Biol.Crystallogr_59_595
Author(s) : Hiramatsu H , Kyono K , Shima H , Fukushima C , Sugiyama S , Inaka K , Yamamoto A , Shimizu R
Ref : Acta Crystallographica D Biol Crystallogr , 59 :595 , 2003
Abstract : Human DPPIV has been expressed in the baculovirus system and purified and crystallized using the hanging-drop method. A crystal was obtained from 180 mM Gly-NaOH buffer pH 9.5 containing 18% PEG 4000 and 180 mM sodium acetate. The crystal belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 118.04, b = 125.92, c = 136.84 A, and diffracts beyond 2.6 A resolution. There are two molecules per asymmetric unit, indicating a solvent content of 57.6%.
ESTHER : Hiramatsu_2003_Acta.Crystallogr.D.Biol.Crystallogr_59_595
PubMedSearch : Hiramatsu_2003_Acta.Crystallogr.D.Biol.Crystallogr_59_595
PubMedID: 12595736