title: Structure-guided activity restoration of the silkworm glutathione transferase Omega GSTO3-3.
abstract: Glutathione transferases (GSTs) are ubiquitous detoxification enzymes that conjugate hydrophobic xenobiotics with reduced glutathione. The silkworm Bombyx mori encodes four isoforms of GST Omega (GSTO), featured with a catalytic cysteine, except that bmGSTO3-3 has an asparagine substitution of this catalytic residue. Here, we determined the 2.20-Å crystal structure of bmGSTO3-3, which shares a typical GST overall structure. However, the extended C-terminal segment that exists in all the four bmGSTOs occupies the G-site of bmGSTO3-3 and makes it unworkable, as shown by the activity assays. Upon mutation of Asn29 to Cys and truncation of the C-terminal segment, the in vitro GST activity of bmGSTO3-3 could be restored. These findings provided structural insights into the activity regulation of GSTOs.
authors.affiliation: School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
authors.forename: Bao-Yu
authors.initials: BY
authors.lastname: Chen
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Ma
authors.forename: Peng-Chao
authors.initials: PC
authors.lastname: Guo
authors.forename: Xiang
authors.initials: X
authors.lastname: Tan
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Li
authors.forename: Jie-Pin
authors.initials: JP
authors.lastname: Yang
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Zhang
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Chen
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Xia
authors.forename: Cong-Zhao
authors.initials: CZ
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D005982:Glutathione Transferase