5Y7J

Crystal structure of human DPP4 in complex with inhibitor2

5Y7J の概要

• エントリーDOI: 10.2210/pdb5y7j/pdb
• 分子名称: Dipeptidyl peptidase 4, (S)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one (3 entities in total)
• 機能のキーワード: dpp4, inhibitor, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 339456.16

構造登録者

Lee, H.K.,Kim, E.E. (登録日: 2017-08-17, 公開日: 2019-03-20, 最終更新日: 2024-10-23)

主引用文献

Lee, H.K.,Kim, M.K.,Kim, H.D.,Kim, H.J.,Kim, J.W.,Lee, J.O.,Kim, C.W.,Kim, E.E.
Unique binding mode of Evogliptin with human dipeptidyl peptidase IV.
Biochem.Biophys.Res.Commun., 494:452-459, 2017

PubMed Abstract: Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S extensive subsite, and that the multiple hydrogen bonds made by the (R)-β-amine group in the S pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin.

PubMed: 29061303
DOI: 10.1016/j.bbrc.2017.10.101

実験手法

X-RAY DIFFRACTION (2.521 Å)