7MSE

High-resolution crystal structure of hMIF2 with tartrate at the active site

7MSE の概要

• エントリーDOI: 10.2210/pdb7mse/pdb
• 分子名称: D-dopachrome decarboxylase, L(+)-TARTARIC ACID (3 entities in total)
• 機能のキーワード: 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: 38230.84

構造登録者

Murphy, E.L.,Manjula, R.,Murphy, J.W.,Lolis, E. (登録日: 2021-05-11, 公開日: 2021-08-18, 最終更新日: 2023-10-18)

主引用文献

Chen, E.,Reiss, K.,Shah, D.,Manjula, R.,Allen, B.,Murphy, E.L.,Murphy, J.W.,Batista, V.S.,Bhandari, V.,Lolis, E.J.,Lisi, G.P.
A structurally preserved allosteric site in the MIF superfamily affects enzymatic activity and CD74 activation in D-dopachrome tautomerase.
J.Biol.Chem., 297:101061-101061, 2021

PubMed Abstract: The macrophage migration inhibitory factor (MIF) family of cytokines contains multiple ligand-binding sites and mediates immunomodulatory processes through an undefined mechanism(s). Previously, we reported a dynamic relay connecting the MIF catalytic site to an allosteric site at its solvent channel. Despite structural and functional similarity, the MIF homolog D-dopachrome tautomerase (also called MIF-2) has low sequence identity (35%), prompting the question of whether this dynamic regulatory network is conserved. Here, we establish the structural basis of an allosteric site in MIF-2, showing with solution NMR that dynamic communication is preserved in MIF-2 despite differences in the primary sequence. X-ray crystallography and NMR detail the structural consequences of perturbing residues in this pathway, which include conformational changes surrounding the allosteric site, despite global preservation of the MIF-2 fold. Molecular simulations reveal MIF-2 to contain a comparable hydrogen bond network to that of MIF, which was previously hypothesized to influence catalytic activity by modulating the strength of allosteric coupling. Disruption of the allosteric relay by mutagenesis also attenuates MIF-2 enzymatic activity in vitro and the activation of the cluster of differentiation 74 receptor in vivo, highlighting a conserved point of control for nonoverlapping functions in the MIF superfamily.

PubMed: 34384784
DOI: 10.1016/j.jbc.2021.101061

実験手法

X-RAY DIFFRACTION (1.27 Å)