7Y4F

bacterial DPP4

Summary for 7Y4F

• Entry DOI: 10.2210/pdb7y4f/pdb
• Descriptor: Dipeptidyl peptidase IV (2 entities in total)
• Functional Keywords: gut microbiota, hydrolase
• Biological source: Bacteroides thetaiotaomicron
• Total number of polymer chains: 4
• Total formula weight: 336756.59

Authors

Hang, J.,Jiang, C.,Wang, K.,Zhang, Z.,Guo, F.,Liu, J.,Wang, G.,Lei, X.,Gonzalez, F.,Qiao, J. (deposition date: 2022-06-14, release date: 2023-06-14, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.918 Å)