3KTL

Crystal Structure of an I71A human GSTA1-1 mutant in complex with S-hexylglutathione

Summary for 3KTL

• Entry DOI: 10.2210/pdb3ktl/pdb
• Related: 2R6K
• Descriptor: Glutathione S-transferase A1, S-HEXYLGLUTATHIONE (3 entities in total)
• Functional Keywords: thioredoxin, s-hexylglutathione, glutathione s-transferase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P08263
• Total number of polymer chains: 2
• Total formula weight: 51778.67

Authors

Achilonu, I.A.,Gildenhuys, S.,Fernandes, M.A.,Fanucchi, S.,Dirr, H.W. (deposition date: 2009-11-25, release date: 2009-12-22, Last modification date: 2023-09-06)

Primary citation

Achilonu, I.,Gildenhuys, S.,Fisher, L.,Burke, J.,Fanucchi, S.,Sewell, B.T.,Fernandes, M.,Dirr, H.W.
The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function.
Acta Crystallogr.,Sect.F, 66:776-780, 2010

PubMed Abstract: The common fold shared by members of the glutathione-transferase (GST) family has a topologically conserved isoleucine residue at the N-terminus of helix 3 which is involved in the packing of helix 3 against two beta-strands in domain 1. The role of the isoleucine residue in the structure, function and stability of GST was investigated by replacing the Ile71 residue in human GSTA1-1 by alanine or valine. The X-ray structures of the I71A and I71V mutants resolved at 1.75 and 2.51 A, respectively, revealed that the mutations do not alter the overall structure of the protein compared with the wild type. Urea-induced equilibrium unfolding studies using circular dichroism and tryptophan fluorescence suggest that the mutation of Ile71 to alanine or valine reduces the stability of the protein. A functional assay with 1-chloro-2,4-dinitrobenzene shows that the mutation does not significantly alter the function of the protein relative to the wild type. Overall, the results suggest that conservation of the topologically conserved Ile71 maintains the structural stability of the protein but does not play a significant role in catalysis and substrate binding.

PubMed: 20606271
DOI: 10.1107/S1744309110019135

Experimental method

X-RAY DIFFRACTION (1.75 Å)