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Structures of yeast glutathione-S-transferase Gtt2 reveal a new catalytic type of GST family.

ABSTRACT: Glutathione-S-transferases (GSTs) are ubiquitous detoxification enzymes that catalyse the conjugation of electrophilic substrates to glutathione. Here, we present the crystal structures of Gtt2, a GST of Saccharomyces cerevisiae, in apo and two ligand-bound forms, at 2.23 A, 2.20 A and 2.10 A, respectively. Although Gtt2 has the overall structure of a GST, the absence of the classic catalytic essential residues--tyrosine, serine and cysteine--distinguishes it from all other cytosolic GSTs of known structure. Site-directed mutagenesis in combination with activity assays showed that instead of the classic catalytic residues, a water molecule stabilized by Ser129 and His123 acts as the deprotonator of the glutathione sulphur atom. Furthermore, only glycine and alanine are allowed at the amino-terminus of helix-alpha1 because of stereo-hindrance. Taken together, these results show that yeast Gtt2 is a novel atypical type of cytosolic GST.

SUBMITTER: Ma XX

PROVIDER: S-EPMC2799204 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Structures of yeast glutathione-S-transferase Gtt2 reveal a new catalytic type of GST family.

Ma Xiao-Xiao XX Jiang Yong-Liang YL He Yong-Xing YX Bao Rui R Chen Yuxing Y Zhou Cong-Zhao CZ

EMBO reports 20091023 12

Glutathione-S-transferases (GSTs) are ubiquitous detoxification enzymes that catalyse the conjugation of electrophilic substrates to glutathione. Here, we present the crystal structures of Gtt2, a GST of Saccharomyces cerevisiae, in apo and two ligand-bound forms, at 2.23 A, 2.20 A and 2.10 A, respectively. Although Gtt2 has the overall structure of a GST, the absence of the classic catalytic essential residues--tyrosine, serine and cysteine--distinguishes it from all other cytosolic GSTs of kno ...[more]

PMID: 19851333

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