A homology model for the human theta-class glutathione transferase T1-1.
A manual threading approach is used to model the human glutathione transferase T1-1 based on the coordinates of the related Theta class enzyme T2-2. The low level of sequence identity (about 20%), found in the C-terminal extension in conjunction with a relative deletion of about five residues makes this a challenging modeling problem. The C-terminal extension contributes to the active site of the molecule and is thus of particular interest for understanding the molecular mechanism of the enzyme. Manual docking of known substrates and non-substrates has implicated potential candidates for the T1-1 catalytic residues involved in the dehalogenation and epoxide-ring opening activities. These include the conserved Theta class residues Arg 107, Trp 115, and the conserved GSTT1 subclass residue His 176. Also, the residue at position 234 is implicated in the modulation of T1-1 activity with different substrates between species.
Flanagan
J U
JU
John Curtin School of Medical Research, Australian National University, Canberra, ACT.
Rossjohn
J
J
Parker
M W
MW
Board
P G
PG
Chelvanayagam
G
G
D000595:Amino Acid Sequence; D000818:Animals; D019281:Dimerization; D005982:Glutathione Transferase / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013379:Substrate Specificity
D005982:Glutathione Transferase