Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1993 Dec;2(12):2095–2102. doi: 10.1002/pro.5560021210

MIF protein are theta-class glutathione S-transferase homologs.

F A Blocki 1, L B Ellis 1, L P Wackett 1
PMCID: PMC2142320  PMID: 8298459

Abstract

MIF proteins are mammalian polypeptides of approximately 13,000 molecular weight. This class includes human macrophage migration inhibitory factor (MIF), a rat liver protein that has glutathione S-transferase (GST) activity (TRANSMIF), and the mouse delayed early response gene 6 (DER6) protein. MIF proteins were previously linked to GSTs by demonstrating transferase activity and observing N-terminal sequence homology with a mu-class GST (Blocki, F.A., Schlievert, P.M., & Wackett, L.P., 1992, Nature 360, 269-270). In this study, MIF proteins are shown to be structurally related to the theta class of GSTs. This is established in three ways. First, unique primary sequence patterns are developed for each of the GST gene classes. The patterns identify the three MIF proteins as theta-like transferase homologs. Second, pattern analysis indicates that GST members of the theta class contain a serine residue in place of the N-terminal tyrosine that is implicated in glutathione deprotonation and activation in GSTs of known structure (Liu, S., et al., 1992, J. Biol. Chem. 267, 4296-4299). The MIF proteins contain a threonine at this position. Third, polyclonal antibodies raised against recombinant human MIF cross-react on Western blots with rat theta GST but not with alpha and mu GSTs. That MIF proteins have glutathione-binding ability may provide a common structural key toward understanding the varied functions of this widely distributed emerging gene family. Because theta is thought to be the most ancient evolutionary GST class, MIF proteins may have diverged early in evolution but retained a glutathione-binding domain.

Full Text

The Full Text of this article is available as a PDF (2.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armstrong R. N. Glutathione S-transferases: reaction mechanism, structure, and function. Chem Res Toxicol. 1991 Mar-Apr;4(2):131–140. doi: 10.1021/tx00020a001. [DOI] [PubMed] [Google Scholar]
  2. Blocki F. A., Schlievert P. M., Wackett L. P. Rat liver protein linking chemical and immunological detoxification systems. Nature. 1992 Nov 19;360(6401):269–270. doi: 10.1038/360269a0. [DOI] [PubMed] [Google Scholar]
  3. Bloom B. R., Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 1966 Jul 1;153(3731):80–82. doi: 10.1126/science.153.3731.80. [DOI] [PubMed] [Google Scholar]
  4. Cunha F. Q., Weiser W. Y., David J. R., Moss D. W., Moncada S., Liew F. Y. Recombinant migration inhibitory factor induces nitric oxide synthase in murine macrophages. J Immunol. 1993 Mar 1;150(5):1908–1912. [PubMed] [Google Scholar]
  5. David J. R. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A. 1966 Jul;56(1):72–77. doi: 10.1073/pnas.56.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Faulkner D. V., Jurka J. Multiple aligned sequence editor (MASE). Trends Biochem Sci. 1988 Aug;13(8):321–322. doi: 10.1016/0968-0004(88)90129-6. [DOI] [PubMed] [Google Scholar]
  7. Gerchman Y., Olami Y., Rimon A., Taglicht D., Schuldiner S., Padan E. Histidine-226 is part of the pH sensor of NhaA, a Na+/H+ antiporter in Escherichia coli. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1212–1216. doi: 10.1073/pnas.90.4.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ji X., Zhang P., Armstrong R. N., Gilliland G. L. The three-dimensional structure of a glutathione S-transferase from the mu gene class. Structural analysis of the binary complex of isoenzyme 3-3 and glutathione at 2.2-A resolution. Biochemistry. 1992 Oct 27;31(42):10169–10184. doi: 10.1021/bi00157a004. [DOI] [PubMed] [Google Scholar]
  9. Kolm R. H., Sroga G. E., Mannervik B. Participation of the phenolic hydroxyl group of Tyr-8 in the catalytic mechanism of human glutathione transferase P1-1. Biochem J. 1992 Jul 15;285(Pt 2):537–540. doi: 10.1042/bj2850537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. La Roche S. D., Leisinger T. Sequence analysis and expression of the bacterial dichloromethane dehalogenase structural gene, a member of the glutathione S-transferase supergene family. J Bacteriol. 1990 Jan;172(1):164–171. doi: 10.1128/jb.172.1.164-171.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lanahan A., Williams J. B., Sanders L. K., Nathans D. Growth factor-induced delayed early response genes. Mol Cell Biol. 1992 Sep;12(9):3919–3929. doi: 10.1128/mcb.12.9.3919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Liu S., Zhang P., Ji X., Johnson W. W., Gilliland G. L., Armstrong R. N. Contribution of tyrosine 6 to the catalytic mechanism of isoenzyme 3-3 of glutathione S-transferase. J Biol Chem. 1992 Mar 5;267(7):4296–4299. [PubMed] [Google Scholar]
  13. Mannervik B., Danielson U. H. Glutathione transferases--structure and catalytic activity. CRC Crit Rev Biochem. 1988;23(3):283–337. doi: 10.3109/10409238809088226. [DOI] [PubMed] [Google Scholar]
  14. Manoharan T. H., Gulick A. M., Reinemer P., Dirr H. W., Huber R., Fahl W. E. Mutational substitution of residues implicated by crystal structure in binding the substrate glutathione to human glutathione S-transferase pi. J Mol Biol. 1992 Jul 20;226(2):319–322. doi: 10.1016/0022-2836(92)90949-k. [DOI] [PubMed] [Google Scholar]
  15. Meyer D. J., Coles B., Pemble S. E., Gilmore K. S., Fraser G. M., Ketterer B. Theta, a new class of glutathione transferases purified from rat and man. Biochem J. 1991 Mar 1;274(Pt 2):409–414. doi: 10.1042/bj2740409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ogura K., Nishiyama T., Okada T., Kajital J., Narihata H., Watabe T., Hiratsuka A., Watabe T. Molecular cloning and amino acid sequencing of rat liver class theta glutathione S-transferase Yrs-Yrs inactivating reactive sulfate esters of carcinogenic arylmethanols. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1294–1300. doi: 10.1016/0006-291x(91)92079-y. [DOI] [PubMed] [Google Scholar]
  17. Orme I. M., Furney S. K., Skinner P. S., Roberts A. D., Brennan P. J., Russell D. G., Shiratsuchi H., Ellner J. J., Weiser W. Y. Inhibition of growth of Mycobacterium avium in murine and human mononuclear phagocytes by migration inhibitory factor. Infect Immun. 1993 Jan;61(1):338–342. doi: 10.1128/iai.61.1.338-342.1993. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  18. Pemble S. E., Taylor J. B. An evolutionary perspective on glutathione transferases inferred from class-theta glutathione transferase cDNA sequences. Biochem J. 1992 Nov 1;287(Pt 3):957–963. doi: 10.1042/bj2870957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Prändl R., Kutchan T. M. Nucleotide Sequence of the Gene for a Glutathione S-Transferase from Cell Suspension Cultures of Silene cucubalus. Plant Physiol. 1992 Aug;99(4):1729–1731. doi: 10.1104/pp.99.4.1729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reinemer P., Dirr H. W., Ladenstein R., Huber R., Lo Bello M., Federici G., Parker M. W. Three-dimensional structure of class pi glutathione S-transferase from human placenta in complex with S-hexylglutathione at 2.8 A resolution. J Mol Biol. 1992 Sep 5;227(1):214–226. doi: 10.1016/0022-2836(92)90692-d. [DOI] [PubMed] [Google Scholar]
  21. Reinemer P., Dirr H. W., Ladenstein R., Schäffer J., Gallay O., Huber R. The three-dimensional structure of class pi glutathione S-transferase in complex with glutathione sulfonate at 2.3 A resolution. EMBO J. 1991 Aug;10(8):1997–2005. doi: 10.1002/j.1460-2075.1991.tb07729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rocklin R. E., Rosen F. S., David J. R. In vitro lymphocyte response of patients with immunologic deficiency diseases. N Engl J Med. 1970 Jun 11;282(24):1340–1343. doi: 10.1056/NEJM197006112822404. [DOI] [PubMed] [Google Scholar]
  23. Scholtz R., Wackett L. P., Egli C., Cook A. M., Leisinger T. Dichloromethane dehalogenase with improved catalytic activity isolated from a fast-growing dichloromethane-utilizing bacterium. J Bacteriol. 1988 Dec;170(12):5698–5704. doi: 10.1128/jb.170.12.5698-5704.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smith R. F., Smith T. F. Pattern-induced multi-sequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling. Protein Eng. 1992 Jan;5(1):35–41. doi: 10.1093/protein/5.1.35. [DOI] [PubMed] [Google Scholar]
  25. Stenberg G., Board P. G., Mannervik B. Mutation of an evolutionarily conserved tyrosine residue in the active site of a human class Alpha glutathione transferase. FEBS Lett. 1991 Nov 18;293(1-2):153–155. doi: 10.1016/0014-5793(91)81174-7. [DOI] [PubMed] [Google Scholar]
  26. Warholm M., Guthenberg C., von Bahr C., Mannervik B. Glutathione transferases from human liver. Methods Enzymol. 1985;113:499–504. doi: 10.1016/s0076-6879(85)13065-x. [DOI] [PubMed] [Google Scholar]
  27. Weiser W. Y., Pozzi L. M., David J. R. Human recombinant migration inhibitory factor activates human macrophages to kill Leishmania donovani. J Immunol. 1991 Sep 15;147(6):2006–2011. [PubMed] [Google Scholar]
  28. Weiser W. Y., Temple P. A., Witek-Giannotti J. S., Remold H. G., Clark S. C., David J. R. Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7522–7526. doi: 10.1073/pnas.86.19.7522. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES