With the support of the Organic Dynamics Program in the Chemistry Division, Professor Giovanna Ghirlanda of Arizona State University will design and study novel functional membrane proteins with tunable properties. As a first step in this direction, a heme-binding site has been engineered into a natural membrane protein, Glycophorin A, which forms stable dimers by the association of its transmembrane helical domain. The initial design, ME1, binds ferric protoporphyrin IX with high affinity, exhibits a redox potential within the range of natural membrane heme-binding proteins, and shows nascent catalytic activity. During the funding period this system will be further investigated and serve as the template for the design of a large library of mutants explicitly designed to optimize heme binding and controlling the redox potential. The library will be used to analyze the importance of the heme environment, its hydrophobicity and the presence of aromatic residues in determining the midpoint potential and the binding affinity within the context of the ME1 scaffold. Building on these results ME1 will be evolved into an artificial enzyme for monooxigenase and peroxidase reactivity.
The Organic and Macromolecular Chemistry Program supports Professor Giovanna Ghirlanda of Arizona State University whose research on membrane-associated proteins is a relatively untapped resource for applications as biosensors and biocatalysts. A deeper understanding of the relationship between protein structure and function in the membrane environment will permit the preparation of artificial miniaturized proteins tailored to specific biological and non-biological applications. Dr. Ghirlanda will partner with an existing program at ASU to implement a comprehensive approach that integrates classroom demonstrations in K-12 schools, undergraduate training, and specialized workshops for teachers. Undergraduates participating in this service learning internship and outreach program will be trained in the PI's lab to perform classroom experiments designed to spark an interest in biotechnology and to explain the underlying concepts in a simple but scientifically sound manner. The program aims at exposing K-12 students from diverse backgrounds to the college experience and providing role models by facilitating contact with college students.
