3LFL

Crystal Structure of human Glutathione Transferase Omega 1, delta 155

Summary for 3LFL

• Entry DOI: 10.2210/pdb3lfl/pdb
• Related: 1eem
• Descriptor: Glutathione S-transferase omega-1, GLUTATHIONE, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (4 entities in total)
• Functional Keywords: glutathione s-transferase omega 1 del155, protein-glutathione complex, n-terminal thioredoxin-like domain, c-terminal alpha-helical domain, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol : P78417
• Total number of polymer chains: 3
• Total formula weight: 83796.92

Authors

Brock, J. (deposition date: 2010-01-18, release date: 2010-11-24, Last modification date: 2024-02-21)

Primary citation

Zhou, H.,Brock, J.,Casarotto, M.G.,Oakley, A.J.,Board, P.G.
Novel folding and stability defects cause a deficiency of human glutathione transferase omega 1.
J.Biol.Chem., 286:4271-4279, 2011

PubMed Abstract: The polymorphic deletion of Glu-155 from human glutathione transferase omega1 (GSTO1-1) occurs in most populations. Although the recombinant ΔGlu-155 enzyme expressed in Escherichia coli is active, the deletion causes a deficiency of the active enzyme in vivo. The crystal structure and the folding/unfolding kinetics of the ΔGlu-155 variant were determined in order to investigate the cause of the rapid loss of the enzyme in human cells. The crystal structure revealed altered packing around the Glu-155 deletion, an increase in the predicted solvent-accessible area and a corresponding reduction in the buried surface area. This increase in solvent accessibility was consistent with an elevated Stern-Volmer constant. The unfolding of both the wild type and ΔGlu-155 enzyme in urea is best described by a three-state model, and there is evidence for the more pronounced population of an intermediate state by the ΔGlu-155 enzymes. Studies using intrinsic fluorescence revealed a free energy change around 14.4 kcal/mol for the wild type compared with around 8.6 kcal/mol for the ΔGlu-155 variant, which indicates a decrease in stability associated with the Glu-155 deletion. Urea induced unfolding of the wild type GSTO1-1 was reversible through an initial fast phase followed by a second slow phase. In contrast, the ΔGlu-155 variant lacks the slow phase, indicating a refolding defect. It is possible that in some conditions in vivo, the increased solvent-accessible area and the low stability of the ΔGlu-155 variant may promote its unfolding, whereas the refolding defect limits its refolding, resulting in GSTO1-1 deficiency.

PubMed: 21106529
DOI: 10.1074/jbc.M110.197822

Experimental method

X-RAY DIFFRACTION (2.1 Å)