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Structures of yeast glutathione‐ S ‐transferase Gtt2 reveal a new catalytic type of GST family
Author(s) -
Ma XiaoXiao,
Jiang YongLiang,
He YongXing,
Bao Rui,
Chen Yuxing,
Zhou CongZhao
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.216
Subject(s) - glutathione , biochemistry , cysteine , serine , saccharomyces cerevisiae , transferase , alanine , yeast , glutathione s transferase , chemistry , mutagenesis , glycine , cytosol , amino acid , biology , enzyme , stereochemistry , mutation , gene
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 Å, 2.20 Å and 2.10 Å, 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‐α1 because of stereo‐hindrance. Taken together, these results show that yeast Gtt2 is a novel atypical type of cytosolic GST.