Glutathione transferase (GST)

Glutathione transferase (GST) is an important detoxification enzyme that occurs in many forms. My mentor for this project is John Tainer.

GST inactivates poisons by chemically bonding them to the tripeptide glutathione, making them soluble so that the body can easily excrete them. For this reason many kinds of GST are found in the liver. Pathogenic parasites also make their own GSTs to help them inactivate the drugs we use to combat them.

Crystals of GST enzymes

In order to determine the atomic structure of a protein by X-ray crystallography, it is first necessary to crystallize the protein. Here are examples of some GST crystals that I have grown. These are viewed with a microscope and are all less than one millimeter in length.

Schistosomal GST

Other GSTs

Atomic structure

Electron density map of a GST inhibitor in the active site of schistosomal GST.

Literature References

M.A. McTigue, D.R. Williams, and J.A. Tainer (1995) 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. 246(1): 21-27

Atomic Coordinates

Crystal structures of many GSTs are available from the Brookhaven Protein Data Bank (PDB). What follows are annotated links to these. The authors' names and original references may be found within the coordinate files.

Mammalian GSTs

Mammalian GSTs have been grouped in to four major classes, termed Alpha, Mu, Pi, and Theta. One of my projects is to deduce the evolutionary relationships among GSTs using information from both primary structures and atomic coordinates.

Alpha-class GSTs

Human GST A1-1 (unliganded form) at 2.50 Å resolution. You may download the atomic coordinates.
Human GST A1-1 R15K mutant in complex with a glutathione/ethacrynic acid conjugate at 2.00 Å resolution. You may download the atomic coordinates.
Human GST A1-1 in complex with S-benzyl glutathione at 2.60 Å resolution. You may download the atomic coordinates.
Human GST A1-1 in complex with ethacrynic acid at 2.70 Å resolution. You may download the atomic coordinates.
Human GST A1-2-1 chimaera G82R mutant at 2.50 Å resolution. You may download the atomic coordinates.
Mouse lung GST A4-4 at 2.90 Å resolution. You may download the atomic coordinates.

Mu-class GSTs

Human muscle GST M2-2 W214F mutant in complex with glutathione at 1.85 Å resolution. You may download the atomic coordinates.
Human muscle GST M2-2 W214F mutant in complex with glutathione at 3.00 Å resolution (different crystal form?). You may download the atomic coordinates.
Human muscle GST M2-2 W214F mutant In complex with glutathione at 3.50 Å resolution (different crystal form?). You may download the atomic coordinates.
Rat liver GST M3-3 in complex with (9S,10S)-9-(S-glutathionyl)-10-hydroxy-9,10-dihrophenanthrene at 1.80 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 in complex with (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9,10-dihrophenanthrene at 1.90 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 in complex with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANION at 1.90 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 in complex with 1-(S-(GLUTATHIONYL)-2,4-DINITROBENZENE at 2.00 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 in complex with glutathione at 2.30 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 T13A mutant in complex with GPS 9-(S-GLUTATHIONYL)-20-HYDROXY-9,10-DIHYDROPHENANTHRENE at 1.85 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 T13S mutant in complex with GPS 9-(S-GLUTATHIONYL)-20-HYDROXY-9,10-DIHYDROPHENANTHRENE at 1.75 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 T13V mutant in complex with GPS 9-(S-GLUTATHIONYL)-20-HYDROXY-9,10-DIHYDROPHENANTHRENE at 1.85 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 Y6F mutant in complex with GPS 9-(S-GLUTATHIONYL)-20-HYDROXY-9,10-DIHYDROPHENANTHRENE at 2.10 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 Y6F mutant in complex with glutathione at 2.20 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 in complex with glutathione at 2.50 Å resolution. You may download the atomic coordinates.
Rat liver GST M3-3 in complex with glutathione at 2.50 Å resolution (another crystal form). You may download the atomic coordinates.

Pi-class GSTs

Human placental GST P1-1 in complex with S-hexyl glutathione at 1.80 Å resolution. You may download the atomic coordinates.
Human placental GST P1-1 in complex with (9R,10R)-9-(S-GLUTATHIONYL)-10-HYDROXY-9,10-DIHYDROPHENANTHRENE at 1.90 Å resolution. You may download the atomic coordinates.
Human placental Pi class GST in complex with glutathione at 1.80 Å resolution. You may download the atomic coordinates.
Human placental Pi class GST in complex with ethacrynic acid at 1.90 Å resolution. You may download the atomic coordinates.
Human placental Pi class GST in complex with a glutathione/ethacrynic acid conjugate at 1.90 Å resolution. You may download the atomic coordinates.
Human placental Pi class GST in complex with p-bromobenzyl glutathione at 1.94 Å resolution. You may download the atomic coordinates.
Human GST P1-1 Y108F mutant at 2.50 Å resolution. You may download the atomic coordinates.
Human placental Pi class GST in complex with Meisenheimer complex at 2.00 Å resolution. You may download the atomic coordinates.
Human placental Pi class GST in complex with S-hexyl glutathione at 2.80 Å resolution. You may download the atomic coordinates.
Mouse Pi class GST with carboxymethylated Cys47 at 2.00 Å resolution. You may download the atomic coordinates.
Mouse Pi class GST in complex with glutathione at 2.40 Å resolution. You may download the atomic coordinates.
Mouse Pi class GST in complex with glutathione sulfonic acid at 1.90 Å resolution. You may download the atomic coordinates.
Mouse liver Pi class GST in complex with S-(p-nitrobenzyl) glutathione at 1.80 Å resolution. You may download the atomic coordinates.
Mouse liver Pi class GST in complex with S-hexyl glutathione at 2.20 Å resolution. You may download the atomic coordinates.
Pig lung Pi class GST in complex with glutathione sulfonate at 2.11 Å resolution. You may download the atomic coordinates.

Non-mammalian GSTs

The class nomenclature for GSTs was originally developed to describe mammalian GSTs. Non-mammalian GSTs frequently show some similarity with one of the mammalian classes, but the nomenclature for this is not yet firmly established.

Chicken GST M1-1 at 1.94 Å resolution. Similar to mammalian Mu class GSTs. You may download the atomic coordinates.
Schistosoma japonicum (parasitic flatworm) 26 kDa GST (unliganded) at 2.4 Å resolution. Similar to mammalian Mu class GSTs. You may download the atomic coordinates.
Schistosoma japonicum (parasitic flatworm) 26 kDa GST in complex with praziquantel at 2.4 Å resolution. Similar to mammalian Mu class GSTs. You may download the atomic coordinates.
Schistosoma japonicum (parasitic flatworm) 26 kDa GST fused to an HIV peptide at 2.5 Å resolution. Similar to mammalian Mu class GSTs. You may download the atomic coordinates.
Arabidopsis thaliana (mouse-ear cress, plant) GST at 2.2 Å resolution. Similar to mammalian Theta class GSTs. You may download the atomic coordinates.
Squid digestive gland GST in complex with S-(3-iodobenzyl) glutathione at 2.2 Å resolution. Called a Sigma class GST. You may download the atomic coordinates.
Squid digestive gland GST in complex with 1-(S-glutathionyl)-2,4-dinitrobenzene at 2.4 Å resolution. Called a Sigma class GST. You may download the atomic coordinates.

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