Synthetic models of metalloenzymes

Reaction Mechanisms of Metalloenzymes and Synthetic Model Complexes Activating Dioxygen Reaction Mechanisms of Metalloenzymes and Synthetic Model Complexes Activating Dioxygen

5. Directed evolution of artificial metalloenzymes: bridging synthetic chemistry and biology

Directed evolution is a powerful algorithm for engineering proteins to have novel and useful properties. However, we do not yet fully understand the characteristics of an evolvable system. In this chapter, we present examples where directed evolution has been used to enhance the performance of metalloenzymes, focusing first on ‘classical’ cases such as improving enzyme stability or expanding th...

Surprising cofactors in metalloenzymes.

Transition metal complexes are located at the active sites of a number of enzymes involved in intriguing biochemical reactions. These complexes can exhibit a wide variety of chemical reactivity due to the ease at which transition metals can adopt different coordination environments and oxidation states. Crystallography has been a powerful technique for examining the structure and conformational...

Designing Hydrolytic Zinc Metalloenzymes

Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for r...

Rational design of nascent metalloenzymes.

Understanding the early genesis of new enzymatic functions is one of the challenges in protein design, mechanistic enzymology, and molecular evolution. We have experimentally mimicked starting points in this process by introducing primitive iron and oxygen binding sites at various locations in thioredoxin, a small protein lacking metal centers, by using computational design. These rudimentary a...