8VFO

Crystal Structure of L117G Variant of D-Dopachrome Tautomerase (D-DT)

8VFO の概要

• エントリーDOI: 10.2210/pdb8vfo/pdb
• 分子名称: D-dopachrome decarboxylase, CITRIC ACID (3 entities in total)
• 機能のキーワード: truncation, enzyme, cytokine, isomerase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12729.55

構造登録者

Parkins, A.,Pilien, A.,Thompson, M.C.,Pantouris, G. (登録日: 2023-12-21, 公開日: 2024-05-01, 最終更新日: 2024-05-22)

主引用文献

Parkins, A.,Pilien, A.V.R.,Wolff, A.M.,Argueta, C.,Vargas, J.,Sadeghi, S.,Franz, A.H.,Thompson, M.C.,Pantouris, G.
The C-terminal Region of D-DT Regulates Molecular Recognition for Protein-Ligand Complexes.
J.Med.Chem., 67:7359-7372, 2024

PubMed Abstract: 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.

PubMed: 38670943
DOI: 10.1021/acs.jmedchem.4c00177

実験手法

X-RAY DIFFRACTION (1.35 Å)