7Y4F

bacterial DPP4

7Y4F の概要

• エントリーDOI: 10.2210/pdb7y4f/pdb
• 分子名称: Dipeptidyl peptidase IV (2 entities in total)
• 機能のキーワード: gut microbiota, hydrolase
• 由来する生物種: Bacteroides thetaiotaomicron
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 336756.59

構造登録者

Hang, J.,Jiang, C.,Wang, K.,Zhang, Z.,Guo, F.,Liu, J.,Wang, G.,Lei, X.,Gonzalez, F.,Qiao, J. (登録日: 2022-06-14, 公開日: 2023-06-14, 最終更新日: 2023-11-29)

主引用文献

Wang, K.,Zhang, Z.,Hang, J.,Liu, J.,Guo, F.,Ding, Y.,Li, M.,Nie, Q.,Lin, J.,Zhuo, Y.,Sun, L.,Luo, X.,Zhong, Q.,Ye, C.,Yun, C.,Zhang, Y.,Wang, J.,Bao, R.,Pang, Y.,Wang, G.,Gonzalez, F.J.,Lei, X.,Qiao, J.,Jiang, C.
Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target.
Science, 381:eadd5787-eadd5787, 2023

PubMed Abstract: A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk. We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.

PubMed: 37535747
DOI: 10.1126/science.add5787

実験手法

X-RAY DIFFRACTION (1.918 Å)