<br>多形拟杆菌中 DPP4 同源物的化学蛋白质组学鉴定,Nature Chemical Biology

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多形拟杆菌中 DPP4 同源物的化学蛋白质组学鉴定
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2023-06-22 , DOI: 10.1038/s41589-023-01357-8
Laura J Keller ₁ , Taylor H Nguyen ₂ , Lawrence J Liu ₃ , Brianna M Hurysz ₃ , Markus Lakemeyer _{4,

5} , Matteo Guerra _{4,

6} , Danielle J Gelsinger ₃ , Rachael Chanin _{7,

8} , Nhi Ngo ₉ , Kenneth M Lum ₉ , Franco Faucher ₁₀ , Phillip Ipock ₄ , Micah J Niphakis ₉ , Ami S Bhatt _{7,

8} , Anthony J O'Donoghue ₃ , Kerwyn Casey Huang _{2,

11,

12} , Matthew Bogyo _{4,

11}

Affiliation

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Bioengineering, Stanford University, Stanford, CA, USA.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich-Schiller-University, Jena, Germany.
Department of Biochemical and Cellular Pharmacology, Genentech, San Francisco, CA, USA.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Divisions of Hematology and Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA, USA.
Lundbeck La Jolla Research Center, Inc., San Diego, CA, USA.
Department of Chemistry, Stanford University, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Chan Zuckerberg Biohub, San Francisco, CA, USA.

丝氨酸水解酶在信号传导和人类代谢中具有重要作用，但对其在肠道共生细菌中的功能知之甚少。利用生物信息学和化学蛋白质组学，我们鉴定了肠道共生多形拟杆菌中的丝氨酸水解酶，这些酶是拟杆菌门特有的。其中两个被预测为人类二肽基肽酶 4 (hDPP4) 的同源物，hDPP4 是调节胰岛素信号传导的关键酶。我们的功能研究表明，BT4193 是 hDPP4 的真正同源物，可以被 FDA 批准的针对 hDPP4 的 2 型糖尿病药物抑制，而另一个是被错误注释的脯氨酸特异性三氨基肽酶。我们证明 BT4193 对于包膜完整性很重要，并且 BT4193 的丢失会降低B. thetaiotaomicron在多样化群落的体外生长过程中的适应性。然而，这两种功能都不依赖于 BT4193 蛋白水解活性，表明这种细菌蛋白酶具有支架或信号传导功能。

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更新日期：2023-06-23

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