Unique binding mode of Evogliptin with human dipeptidyl peptidase IV
- Authors
- Lee, Hyung Ki; Kim, Mi-Kyung; Kim, Ha Dong; Kim, Heung Jae; Kim, Ji Won; Lee, Jie-Oh; Kim, Chan-Wha; Kim, Eunice EunKyeong
- Issue Date
- 16-12월-2017
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Dipeptidyl peptidase IV; DPP4; Evogliptin; Diabetes; Inhibitor; Complex structure
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.494, no.3-4, pp.452 - 459
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 494
- Number
- 3-4
- Start Page
- 452
- End Page
- 459
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/81160
- DOI
- 10.1016/j.bbrc.2017.10.101
- ISSN
- 0006-291X
- 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-1 pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S-2 extensive subsite, and that the multiple hydrogen bonds made by the (R)-beta-amine group in the S-2 pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin. (c) 2017 Elsevier Inc. All rights reserved.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Life Sciences and Biotechnology > Division of Life Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.