Structures of yeast glutathione-S-transferase Gtt2 reveal a new catalytic type of GST family.
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.
Ma
Xiao-Xiao
XX
Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
Jiang
Yong-Liang
YL
He
Yong-Xing
YX
Bao
Rui
R
Chen
Yuxing
Y
Zhou
Cong-Zhao
CZ
D000595:Amino Acid Sequence; D002384:Catalysis; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D050505:Mutant Proteins; D005982:Glutathione Transferase