Description:
Investigators at Colorado State University have discovered a new form of a non-covalent interaction, which is named a hydrogen bond enhanced halogen bond (or HeX-B, for short). The HeX-B was engineered into the enzyme lysozyme to increase the thermal stability of a commonly used enzyme by 1°C and the activity by 15% at elevated temperatures relative to the native enzyme. This interaction can be used to increase the stability of enzymes and proteins by 1 to 3.5 kcal/mol. This interaction, therefore, can be translated to significant increases in stability of proteins at high temperatures for biomolecular engineering halogenated proteins and nucleic acids. This process can also increase the affinity of an inhibitor or drug against therapeutic targets by 5 to >300-fold when designing new halogenated compounds for clinical use.
Advantages Over State Of The Art:
Current state-of-the-art relies on stand alone, classical halogen bonding interactions, which can provide 1 to 6 kcal/mol of stabilizing energy, which translates to significant increases in thermal stability of molecules and in affinity for halogenated compounds.
Figure 1 - Enzymatic activities of constructs, as a percent of the Wild Type activity, at 23°C and 40°C.
