A surface mutant (G82R) of a human α‐glutathione S‐transferase shows decreased thermal stability and a new mode of molecular association in the crystal

A chimeric enzyme (GST121) of the human α‐glutathione S‐transferases GST1‐1 and GST2‐2, which has improved catalytic efficiency and thermostability from its wild‐type parent proteins, has been crystallized in a space group that is isomorphous with that reported for crystals of GST1‐1. However, a single‐site (G82R) mutant of GST121, which exhibits a significant reduction both in vitro and in vivo in protein thermostability, forms crystals that are not isomorphous with GST1‐1. The mutant protein crystallizes in space group P2 1 2 1 2 1 , with cell dimensions a = 49.5, b = 92.9, c = 115.9 Å, and one dimer per asymmetric unit. Preliminary crystallographic results show that a mutation of the surface residue Gly 82 from a neutral to a charged residue causes new salt bridges to be formed among the GST dimers, suggesting that the G82R mutant might aggregate more readily than does GST121 in solution resulting in a change of its solution properties. © 1994 Wiley‐Liss, Inc.