Lee A Solomon

University of Pennsylvania | UP · Department of Biochemistry and Biophysics

Oxidoreductases have evolved over millions of years to perform a variety of metabolic tasks crucial for life. Understanding how these tasks are engineered relies on delivering external electron donors or acceptors to initiate electron transfer reactions. This is a challenge. Small-molecule redox reagents can act indiscriminately, poisoning the cell...

Natural selection in photosynthesis has engineered tetrapyrrole based, nanometer scale, light harvesting and energy capture in light-induced charge separation. By designing and creating nanometer scale artificial light harvesting and charge separating proteins, we have the opportunity to reengineer and overcome the limitations of natural selection...

Maquettes are man-made cofactor-binding oxidoreductases designed from first principles with minimal reference to natural protein sequences. Here we focus on water-soluble maquettes designed and engineered to perform diffusive electron transport of the kind typically carried out by cytochromes, ferredoxins and flavodoxins and other small proteins in...

Timely ligation of one or more chemical cofactors at preselected locations in proteins is a critical preamble for catalysis in many natural enzymes, including the oxidoreductases and allied transport and signaling proteins. Likewise, ligation strategies must be directly addressed when designing oxidoreductase and molecular transport functions in ma...

Emulating functions of natural enzymes in man-made constructs has proven challenging. Here we describe a man-made protein platform that reproduces many of the diverse functions of natural oxidoreductases without importing the complex and obscure interactions common to natural proteins. Our design is founded on an elementary, structurally stable 4-α...

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Many key biological functions are accomplished through complicated system of oxidoreductases. Even though a significant number of these enzymes have been structurally characterized, attempts to reproduce their functions have not been successful. This work examines engineering of a simplified 4-alpha-helix-bundle protein, called a maquette, which la...

We have designed a simple protein, monomeric four-α-helix bundle, which can serve as a platform for diverse set of oxidoreductase related functions. We describe the progressive design steps taken from the simplest α-helical peptide toward functionalized proteins. This platform has considerable latitude for external charge patterning and internal co...

Electron transport chain (ETC) modularity inspires framework for renewable energy harvesting. In order to design maquettes capable of light-harvesting and light activated electron transfer using natural and synthetic Zn porphyrins, chlorins and bacteriochlorins, we have explored cofactor structural requirements for binding to the maquettes. Binding...

The study of natural enzymes is complicated by the fact that only the most recent evolutionary progression can be observed. In particular, natural oxidoreductases stand out as profoundly complex proteins in which the molecular roots of function, structure and biological integration are collectively intertwined and individually obscured. In the pres...

The principles of natural protein engineering are obscured by overlapping functions and complexity accumulated through natural selection and evolution. Completely artificial proteins offer a clean slate on which to define and test these protein engineering principles, while recreating and extending natural functions. Here we introduce this method w...