Enzyme catalysis from improved packing in their transition-state structures

The binding of ligands to proteins can be enhanced through improved packing within the proteins that may, or may not, occur with conformational change. Enzymes can similarly improve their catalytic magic through better packing in the transition state (TS) for reaction. In principle, the improved packing demands no more than the minute shortening of non-covalent interactions throughout much of the structure of the protein (positively cooperative binding). Improved protein packing can account for the remarkably high biotin/streptavidin affinity, and perhaps also for a major part of the catalytic function of hypoxanthine-guanine phosphoribosyltransferase and purine nucleoside phosphorylase (PNP). As successive NAD(+) molecules bind to the glyceraldehyde phosphate dehydrogenase tetramer, they do so with positively cooperative binding (using the term as applied in crystallization and protein folding) that decreases at each step. This binding is negatively cooperative in the usage stemming from Monod and co-workers.