The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function.

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Achilonu I, Gildenhuys S, Fisher L, Burke J, Fanucchi S, Sewell BT, Fernandes M, Dirr HW

The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function.

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Jul 1;66(Pt 7):776-80. doi: 10.1107/S1744309110019135. Epub 2010 Jun 23.

PubMed ID

20606271 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
S-Hexylglutathione	Glutathione S-transferase A1	Protein	Humans	Unknown	Ligand	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
S-Hexylglutathione	Glutathione S-transferase A1	Protein	Humans	Unknown	Ligand	Details

Polypeptides

Name	UniProt ID
Glutathione S-transferase A1	P08263	Details