6C5F

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

Summary for 6C5F

• Entry DOI: 10.2210/pdb6c5f/pdb
• Descriptor: D-dopachrome decarboxylase, 4-(3-carboxyphenyl)pyridine-2,5-dicarboxylic acid (3 entities in total)
• Functional Keywords: selective inhibitor, cytokine
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 38067.80

Authors

Pantouris, G.,Lolis, E.J. (deposition date: 2018-01-16, release date: 2018-06-13, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.4 Å)