A SURFACE MUTANT (G82R) OF A HUMAN ALPHA-GLUTATHIONE S-TRANSFERASE SHOWS DECREASED THERMAL-STABILITY AND A NEW MODE OF MOLECULAR ASSOCIATION IN THE CRYSTAL

A chimeric enzyme (GST121) of the human alpha-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 Angstrom, 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. (C) 1994 Wiley-Liss, Inc.