化学
终端(电信)
配体(生物化学)
立体化学
生物化学
受体
计算机网络
计算机科学
作者
A. S. Parkins,Aliyah Veronica R. Pilien,Alexander M. Wolff,Christopher Argueta,Julie S. Vargas,S. Maryam Sadeghi,Andreas H. Franz,Michael C. Thompson,Georgios Pantouris
标识
DOI:10.1021/acs.jmedchem.4c00177
摘要
Systematic analysis of molecular recognition is critical for understanding the biological function of macromolecules. For the immunomodulatory protein D-dopachrome tautomerase (D-DT), the mechanism of protein-ligand interactions is poorly understood. Here, 17 carefully designed protein variants and wild type (WT) D-DT were interrogated with an array of complementary techniques to elucidate the structural basis of ligand recognition. Utilization of a substrate and two selective inhibitors with distinct binding profiles offered previously unseen mechanistic insights into D-DT-ligand interactions. Our results demonstrate that the C-terminal region serves a key role in molecular recognition via regulation of the active site opening, protein-ligand interactions, and conformational flexibility of the pocket's environment. While our study is the first comprehensive analysis of molecular recognition for D-DT, the findings reported herein promote the understanding of protein functionality and enable the design of new structure-based drug discovery projects.
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