4TRF

Crystal structure of Macrophage Migration Inhibitory Factor in complex with N-(pyridin-3-ylmethyl)thioformamide

Summary for 4TRF

• Entry DOI: 10.2210/pdb4trf/pdb
• Related: 4TRS 4TRU
• Descriptor: Macrophage migration inhibitory factor, N-(pyridin-3-ylmethyl)thioformamide, SULFATE ION, ... (6 entities in total)
• Functional Keywords: inhibitor isomerase, complex, active site, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted : P14174
• Total number of polymer chains: 3
• Total formula weight: 38114.39

Authors

Pantouris, G.,Lolis, E. (deposition date: 2014-06-16, release date: 2015-09-30, Last modification date: 2024-10-16)

Primary citation

Pantouris, G.,Syed, M.A.,Fan, C.,Rajasekaran, D.,Cho, T.Y.,Rosenberg, E.M.,Bucala, R.,Bhandari, V.,Lolis, E.J.
An Analysis of MIF Structural Features that Control Functional Activation of CD74.
Chem.Biol., 22:1197-1205, 2015

PubMed Abstract: For more than 15 years, the tautomerase active site of macrophage migration inhibitory factor (MIF) and its catalytic residue Pro1 have been being targeted for the development of therapeutics that block activation of its cell surface receptor, CD74. Neither the biological role of the MIF catalytic site nor the mechanistic details of CD74 activation are well understood. The inherently unstable structure of CD74 remains the biggest obstacle in structural studies with MIF for understanding the basis of CD74 activation. Using a novel approach, we elucidate the mechanistic details that control activation of CD74 by MIF surface residues and identify structural parameters of inhibitors that reduce CD74 biological activation. We also find that N-terminal mutants located deep in the catalytic site affect surface residues immediately outside the catalytic site, which are responsible for reduction of CD74 activation.

PubMed: 26364929
DOI: 10.1016/j.chembiol.2015.08.006

Experimental method

X-RAY DIFFRACTION (1.63 Å)