A HOMOLOGY MODEL FOR THE HUMAN THETA-CLASS GLUTATHIONE TRANSFERASE T1-1

A manual threading approach is used to model the human glutathione tra nsferase T1-1 based on the coordinates of the related Theta class enzy me 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-termina l extension contributes to the active site of the molecule and is thus of particular interest for understanding the molecular mechanism of t he enzyme, Manual docking of known substrates and non-substrates has i mplicated potential candidates for the T1-1 catalytic residues involve d in the dehalogenation and epoxide-ring opening activities. These inc lude the conserved Theta class residues Arg 107, Trp 115, and the cons erved GSTT1 subclass residue His 176, Also, the residue at position 23 4 is implicated in the modulation of T1-1 activity with different subs trates between species. Proteins 33:444-454, 1998, (C) 1998 Wiley-Liss , Inc.