6C5F

Human D-Dopachrome tautomerase (D-DT)/ macrophage migration inhibitory factor 2 (MIF2) complexed with the selective inhibitor 4-CPPC

6C5F の概要

• エントリーDOI: 10.2210/pdb6c5f/pdb
• 分子名称: D-dopachrome decarboxylase, 4-(3-carboxyphenyl)pyridine-2,5-dicarboxylic acid (3 entities in total)
• 機能のキーワード: selective inhibitor, cytokine
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 38067.80

構造登録者

Pantouris, G.,Lolis, E.J. (登録日: 2018-01-16, 公開日: 2018-06-13, 最終更新日: 2023-10-04)

主引用文献

Pantouris, G.,Bucala, R.,Lolis, E.J.
Structural Plasticity in the C-Terminal Region of Macrophage Migration Inhibitory Factor-2 Is Associated with an Induced Fit Mechanism for a Selective Inhibitor.
Biochemistry, 57:3599-3605, 2018

PubMed Abstract: We report the first reversible and selective small molecule inhibitor of pro-inflammatory protein macrophage migration inhibitory factor-2 (also known as MIF-2 or d-DT). 4-(3-Carboxyphenyl)-2,5-pyridinedicarboxylic acid (4-CPPC) shows competitive binding with a 13-fold selectivity for human MIF-2 versus human MIF-1. The crystal structure of MIF-2 complexed with 4-CPPC reveals an induced fit mechanism that is not observed in the numerous MIF-1/inhibitor complexes. Crystallographic analysis demonstrates the structural source of 4-CPPC binding and selectivity for MIF-2. 4-CPPC can be employed to reveal previously unrecognized functions of MIF-1 in biological systems in which both MIF-1 and MIF-2 are expressed, to improve our knowledge of the MIF family of proteins, and to provide new mechanistic insights that can be utilized for the development of potent and selective pharmacological modulators of MIF-2.

PubMed: 29847104
DOI: 10.1021/acs.biochem.8b00344

実験手法

X-RAY DIFFRACTION (1.4 Å)