Patents

The invention deals with examination of the alterability of part, or whole, of the surfaces of beta sheet-based protein structures, focusing especially on enzymes. The alteration is done by supplanting/transplanting a part, or whole, of the surface of one protein onto the surface of a homologous protein of superimposable popypeptide backbone, by exploiting the structural features of beta sheets to alter only the regions of the surface involved in substrate/ligand binding and catalysis. The transplantation involves replacement of a selected set of non-contiguous residues constituting the surface regions desired to be altered in one enzyme/protein, by a set of non-contiguous residues located at analogous positions in the other enzyme/protein, in a manner that is likely to facilitate folding and function of the new chimera formed by combining residues from both enzymes/proteins. The invention also deals with using this surface engineering approach to selectively combine enzyme/protein characteristics from different domains of life that are not ordinarily combined by natural evolution, such as the creation of chimera that retains the bulk of the thermostable scaffold of a thermophile enzyme onto which the active surface of a mesophile homolog is transplanted, so as to create a thermo-stable protein with meso-active functional characteristics of pH and temperature of optimal function.