STRUCTURAL AND MUTATIONAL ANALYSIS OF PROTEIN STABILITY. Brian W. Matthews, Xuejun Zhang, Jian Xu and Walter A. Baase, Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403

Information on the structural basis for protein stability has come from two different sources. (1) Comparisons of the structures of proteins isolated from thermophiles with their counterparts in mesophiles. (2) Analysis of changes in the structure and stability of a given protein associated with point mutations. Conclusions from Source (1) have, however, been inconsistent. Some investigators have suggested that thermostability can come from a variety of sources including the hydrophobic effect, disulfide bridges, hydrogen bonds, metal binding and electrostatic interactions. Others have suggested that one type of interaction or effect (in particular, salt bridges) is key. The use of experiments from Source (2) to attempt to resolve these apparent discrepancies will be discussed.