2XCZ

Crystal Structure of macrophage migration inhibitory factor homologue from Prochlorococcus marinus

2XCZ の概要

• エントリーDOI: 10.2210/pdb2xcz/pdb
• 分子名称: POSSIBLE ATLS1-LIKE LIGHT-INDUCIBLE PROTEIN, DI(HYDROXYETHYL)ETHER (3 entities in total)
• 機能のキーワード: cytokine, tautomerase, immune system, cyanobacterium
• 由来する生物種: PROCHLOROCOCCUS MARINUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12486.17

構造登録者

Wasiel, A.A.,Rozeboom, H.J.,Hauke, D.,Baas, B.J.,Zandvoort, E.,Quax, W.J.,Thunnissen, A.M.W.H.,Poelarends, G.J. (登録日: 2010-04-27, 公開日: 2010-09-01, 最終更新日: 2023-12-20)

主引用文献

Wasiel, A.A.,Rozeboom, H.J.,Hauke, D.,Baas, B.J.,Zandvoort, E.,Quax, W.J.,Thunnissen, A.M.W.H.,Poelarends, G.J.
Structural and Functional Characterization of a Macrophage Migration Inhibitory Factor Homologue from the Marine Cyanobacterium Prochlorococcus Marinus.
Biochemistry, 49:7572-, 2010

PubMed Abstract: Macrophage migration inhibitory factor (MIF) is a multifunctional mammalian cytokine, which exhibits tautomerase and oxidoreductase activity. MIF homologues with pairwise sequence identities to human MIF ranging from 31% to 41% have been detected in various cyanobacteria. The gene encoding the MIF homologue from the marine cyanobacterium Prochlorococcus marinus strain MIT9313 has been cloned and the corresponding protein (PmMIF) overproduced, purified, and subjected to functional and structural characterization. Kinetic and (1)H NMR spectroscopic studies show that PmMIF tautomerizes phenylenolpyruvate and (p-hydroxyphenyl)enolpyruvate at low levels. The N-terminal proline of PmMIF is critical for these reactions because the P1A mutant has strongly reduced tautomerase activities. PmMIF shows high structural homology with mammalian MIFs as revealed by a crystal structure of PmMIF at 1.63 A resolution. MIF contains a Cys-X-X-Cys motif that mediates oxidoreductase activity, which is lacking from PmMIF. Engineering of the motif into PmMIF did not result in oxidoreductase activity but increased the tautomerase activity 8-fold. The shared tautomerase activities and the conservation of the beta-alpha-beta structural fold and key functional groups suggest that eukaryotic MIFs and cyanobacterial PmMIF are related by divergent evolution from a common ancestor. While several MIF homologues have been identified in eukaryotic parasites, where they are thought to play a role in modulating the host immune response, PmMIF is the first nonparasitic, bacterial MIF-like protein characterized in detail. This work sets the stage for future studies which could address the question whether a MIF-like protein from a free-living bacterium possesses immunostimulatory features similar to those of mammalian MIFs and MIF-like proteins found in parasitic nematodes and protozoa.

PubMed: 20715791
DOI: 10.1021/BI1008276

実験手法

X-RAY DIFFRACTION (1.64 Å)