Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Aug 6;93(16):8208–8213. doi: 10.1073/pnas.93.16.8208

Location of a potential transport binding site in a sigma class glutathione transferase by x-ray crystallography.

X Ji 1, E C von Rosenvinge 1, W W Johnson 1, R N Armstrong 1, G L Gilliland 1
PMCID: PMC38648  PMID: 8710848

Abstract

The crystal structure of the sigma class glutathione transferase from squid digestive gland in complex with S-(3-iodobenzyl)glutathione reveals a third binding site for the glutathione conjugate besides the two in the active sites of the dimer. The additional binding site is near the crystallographic two-fold axis between the two alpha 4-turn-alpha 5 motifs. The principal binding interactions with the conjugate include specific electrostatic interactions between the peptide and the two subunits and a hydrophobic cavity found across the two-fold axis that accommodates the 3-iodobenzyl group. Thus, two identical, symmetry-related but mutually exclusive binding modes for the third conjugate are observed. The hydrophobic pocket is about 14 A from the hydroxyl group of Tyr-7 in the active site. This site is a potential transport binding site for hydrophobic molecules or their glutathione conjugates.

Full text

PDF
8211

Images in this article

8212Fig. 6
on p.8212

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. Armstrong R. N. Glutathione S-transferases: structure and mechanism of an archetypical detoxication enzyme. Adv Enzymol Relat Areas Mol Biol. 1994;69:1–44. doi: 10.1002/9780470123157.ch1. [DOI] [PubMed] [Google Scholar]
  3. Dirr H., Reinemer P., Huber R. X-ray crystal structures of cytosolic glutathione S-transferases. Implications for protein architecture, substrate recognition and catalytic function. Eur J Biochem. 1994 Mar 15;220(3):645–661. doi: 10.1111/j.1432-1033.1994.tb18666.x. [DOI] [PubMed] [Google Scholar]
  4. García-Sáez I., Párraga A., Phillips M. F., Mantle T. J., Coll M. Molecular structure at 1.8 A of mouse liver class pi glutathione S-transferase complexed with S-(p-nitrobenzyl)glutathione and other inhibitors. J Mol Biol. 1994 Apr 1;237(3):298–314. doi: 10.1006/jmbi.1994.1232. [DOI] [PubMed] [Google Scholar]
  5. Ishigaki S., Abramovitz M., Listowsky I. Glutathione-S-transferases are major cytosolic thyroid hormone binding proteins. Arch Biochem Biophys. 1989 Sep;273(2):265–272. doi: 10.1016/0003-9861(89)90483-9. [DOI] [PubMed] [Google Scholar]
  6. Ji X., Armstrong R. N., Gilliland G. L. Snapshots along the reaction coordinate of an SNAr reaction catalyzed by glutathione transferase. Biochemistry. 1993 Dec 7;32(48):12949–12954. doi: 10.1021/bi00211a001. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Ji X., von Rosenvinge E. C., Johnson W. W., Tomarev S. I., Piatigorsky J., Armstrong R. N., Gilliland G. L. Three-dimensional structure, catalytic properties, and evolution of a sigma class glutathione transferase from squid, a progenitor of the lens S-crystallins of cephalopods. Biochemistry. 1995 Apr 25;34(16):5317–5328. doi: 10.1021/bi00016a003. [DOI] [PubMed] [Google Scholar]
  9. Jones T. A., Zou J. Y., Cowan S. W., Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991 Mar 1;47(Pt 2):110–119. doi: 10.1107/s0108767390010224. [DOI] [PubMed] [Google Scholar]
  10. Lim K., Ho J. X., Keeling K., Gilliland G. L., Ji X., Rüker F., Carter D. C. Three-dimensional structure of Schistosoma japonicum glutathione S-transferase fused with a six-amino acid conserved neutralizing epitope of gp41 from HIV. Protein Sci. 1994 Dec;3(12):2233–2244. doi: 10.1002/pro.5560031209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Listowsky I., Abramovitz M., Homma H., Niitsu Y. Intracellular binding and transport of hormones and xenobiotics by glutathione-S-transferases. Drug Metab Rev. 1988;19(3-4):305–318. doi: 10.3109/03602538808994138. [DOI] [PubMed] [Google Scholar]
  12. Litwack G., Ketterer B., Arias I. M. Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature. 1971 Dec 24;234(5330):466–467. doi: 10.1038/234466a0. [DOI] [PubMed] [Google Scholar]
  13. Mannervik B., Alin P., Guthenberg C., Jensson H., Tahir M. K., Warholm M., Jörnvall H. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7202–7206. doi: 10.1073/pnas.82.21.7202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McTigue M. A., Williams D. R., Tainer J. A. Crystal structures of a schistosomal drug and vaccine target: glutathione S-transferase from Schistosoma japonica and its complex with the leading antischistosomal drug praziquantel. J Mol Biol. 1995 Feb 10;246(1):21–27. doi: 10.1006/jmbi.1994.0061. [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. Murzin A. G., Brenner S. E., Hubbard T., Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995 Apr 7;247(4):536–540. doi: 10.1006/jmbi.1995.0159. [DOI] [PubMed] [Google Scholar]
  17. Raghunathan S., Chandross R. J., Kretsinger R. H., Allison T. J., Penington C. J., Rule G. S. Crystal structure of human class mu glutathione transferase GSTM2-2. Effects of lattice packing on conformational heterogeneity. J Mol Biol. 1994 May 20;238(5):815–832. doi: 10.1006/jmbi.1994.1336. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Rushmore T. H., Pickett C. B. Glutathione S-transferases, structure, regulation, and therapeutic implications. J Biol Chem. 1993 Jun 5;268(16):11475–11478. [PubMed] [Google Scholar]
  21. Satow Y., Cohen G. H., Padlan E. A., Davies D. R. Phosphocholine binding immunoglobulin Fab McPC603. An X-ray diffraction study at 2.7 A. J Mol Biol. 1986 Aug 20;190(4):593–604. doi: 10.1016/0022-2836(86)90245-7. [DOI] [PubMed] [Google Scholar]
  22. Sinning I., Kleywegt G. J., Cowan S. W., Reinemer P., Dirr H. W., Huber R., Gilliland G. L., Armstrong R. N., Ji X., Board P. G. Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes. J Mol Biol. 1993 Jul 5;232(1):192–212. doi: 10.1006/jmbi.1993.1376. [DOI] [PubMed] [Google Scholar]
  23. Wilce M. C., Board P. G., Feil S. C., Parker M. W. Crystal structure of a theta-class glutathione transferase. EMBO J. 1995 May 15;14(10):2133–2143. doi: 10.1002/j.1460-2075.1995.tb07207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wilce M. C., Parker M. W. Structure and function of glutathione S-transferases. Biochim Biophys Acta. 1994 Mar 16;1205(1):1–18. doi: 10.1016/0167-4838(94)90086-8. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES