Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1.54 Å resolution

被引:108
|
作者
Sugimoto, H
Taniguchi, M
Nakagawa, A
Tanaka, I [1 ]
Suzuki, M
Nishihira, J
机构
[1] Hokkaido Univ, Grad Sch Sci, Div Biol Sci, Sapporo, Hokkaido 0600810, Japan
[2] Hokkaido Univ, Sch Med, Cent Res Inst, Sapporo, Hokkaido 0600815, Japan
关键词
D O I
10.1021/bi982184o
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
D-Dopachrome tautomerase shares a low homologous amino acid sequence (33% homology) with the macrophage migration inhibitory factor (MIF) and possesses similar tautomerase activity as well. MIF is a cytokine involved in inflammatory reactions and immune responses. Whereas recent studies have identified MIF as a pituitary hormone and immunoregulator, much less is known about the structural basis of these physiological functions and the real significance of tautomerase activity. Therefore, interest in the structure-function relationship between D-dopachrome tautomerase and MIF has increased, especially with regard to inflammation and immune responses. We have determined the X-ray crystal structure of human D-dopachrome tautomerase at 1.54 Angstrom resolution, D-Dopachrome tautomerase folds to form a homotrimer that has extensive contact between subunits by intersubunit beta-sheets. Its overall topology and trimeric formations are similar to those of human MTF. The N-terminal proline is located at the bottom of a positively charged pocket in which the conformations of Lys32 and Ser63 are highly conserved. These positively charged properties are also seen in the active site pocket of human MTF, bacterial 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), and 4-oxalocrotonate tautomerase (4-OT), A detailed comparison of these structures revealed significant differences in the environment around the potential active site, the intersubunit contacts, and charge distribution on the molecular surface. It can be concluded that these features are related to the physiological role and tautomerase activity of MIF and D-dopachrome tautomerase. The present structural study could be helpful for designing effective inhibitors that modulate immunoregulatory and hormone-like effects.
引用
收藏
页码:3268 / 3279
页数:12
相关论文
共 50 条
  • [21] Macrophage migration inhibitory factor (MIF) but not its homologue D-dopachrome tautomerase (D-DT) promotes fibroblast motility in a CD44/CD74-independent manner
    Szczesniak, Pawel
    Meinhardt, Andreas
    Klug, Joerg
    FASEB JOURNAL, 2017, 31
  • [22] UVB-induced inflammation gives increased D-dopachrome tautomerase activity in blister fluid which correlates with macrophage migration inhibitory factor
    Sonesson, B
    Rosengren, E
    Hansson, AS
    Hansson, C
    EXPERIMENTAL DERMATOLOGY, 2003, 12 (03) : 278 - 282
  • [23] D-dopachrome tautomerase is over-expressed in pancreatic ductal adenocarcinoma and acts cooperatively with macrophage migration inhibitory factor to promote cancer growth
    Guo, Dawei
    Guo, Jinshuai
    Yao, Junchao
    Jiang, Kun
    Hu, Jianhua
    Wang, Bo
    Liu, Haiyang
    Lin, Lin
    Sun, Wenyu
    Jiang, Xiaofeng
    INTERNATIONAL JOURNAL OF CANCER, 2016, 139 (09) : 2056 - 2067
  • [24] D-dopachrome tautomerase from Japanese sea bass (Lateolabrax japonicus) is a chemokine-like cytokine and functional homolog of macrophage migration inhibitory factor
    Xu, Feng
    Li, Ming-Yun
    Chen, Jiong
    ZOOLOGICAL RESEARCH, 2020, 41 (01) : 39 - 50
  • [25] Shared Single Nucleotide Polymorphisms Regulate Gene Expression of Macrophage Migration Inhibitory Factor and D-Dopachrome Tautomerase-Like Protein in Lung Tissue
    Sampedro, L. Florez
    Brandsma, C. A.
    De Vries, M.
    Timens, W.
    Obeidat, M.
    Joubert, P.
    Nickle, D. C.
    Poelarends, G. J.
    Faiz, A.
    Melgert, B. N.
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2019, 199
  • [26] Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase
    Coleman, Arlixer M.
    Rendon, Beatriz E.
    Zhao, Ming
    Qian, Ming-Wei
    Bucala, Richard
    Xin, Dan
    Mitchell, Robert A.
    JOURNAL OF IMMUNOLOGY, 2008, 181 (04): : 2330 - 2337
  • [27] UVB-induced inflammation gives increased D-Dopachrome tautomerase activity in blister fluid, which correlates with macrophage migration inhibitory factor (MIF).
    Sonesson, B
    Rosengren, E
    Hanson, AS
    Hansson, C
    CLINICAL IMMUNOLOGY, 2002, 103 (03) : S13 - S14
  • [28] The chemokines MIF (macrophage migration inhibitory factor) and MIF-2/DDT (D-dopachrome tautomerase) as key mediators in the pathogenesis of cutaneous squamous cell carcinoma
    Skazik, C.
    Heise, R.
    Czaja, K.
    Marquardt, Y.
    Dewor, M.
    Merk, H. F.
    Fingerle-Rowson, G.
    Bernhagen, J.
    Baron, J. M.
    EXPERIMENTAL DERMATOLOGY, 2015, 24 (03) : E35 - E36
  • [29] D-dopachrome tautomerase from Japanese sea bass(Lateolabrax japonicus) is a chemokine-like cytokine and functional homolog of macrophage migration inhibitory factor附视频
    Feng Xu
    MingYun Li
    Jiong Chen
    Zoological Research, 2020, (01) : 39 - 50