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-transferas es GST1-1 and GST2-2, which has improved catalytic efficiency and ther mostability from its wild-type parent proteins, has been crystallized in a space group that is isomorphous with that reported for crystals o f GST1-1. However, a single-site (G82R) mutant of GST121, which exhibi ts a significant reduction both in vitro and in vivo in protein thermo stability, forms crystals that are not isomorphous with GST1-1, The mu tant protein crystallizes in space group P2(1)2(1)2(1), with cell dime nsions a = 49.5, b = 92.9, c = 115.9 Angstrom, and one dimer per asymm etric unit, Preliminary crystallographic results show that a mutation of the surface residue Gly 82 from a neutral to a charged residue caus es new salt bridges to be formed among the GST dimers, suggesting that the G82R mutant might aggregate more readily than does GST121 in solu tion, resulting in a change of its solution properties. (C) 1994 Wiley -Liss, Inc.