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Yi Lu Professor of Chemistry, Biochemistry, and Biophysics Ph.D. 1992, University of California Metalloprotein Design and Engineering; New catalytic DNA and RNA as Anti-viral Pharmaceutical Agents or as Metal Biosensors Yi Lu A323/325 CLSL, Box 8-6, MC-712 601 S. Goodwin Urbana, IL 61801 217-333-2619 yi-lu@uiuc.edu

Research Goals

The goals of my research group are to elucidate the role of metal ions in proteins, DNAs and RNAs with enzymatic function (called deoxyribozymes and ribozymes, respectively), to design metalloenzymes with novel structures and functions, and to explore the use of the enzymes in biotechnological and pharmaceutical applications. To achieve these goals, we are using and developing many biophysical techniques including bioinformatic analysis of protein and nucleic acid sequences and structures, protein design using automated search algorithms, study of the designed protein or DNA/RNA enzymes using spectroscopic techniques such as electron absorption, magnetic circular dichroism, resonance Raman, fluorescence, electron spin resonance, nuclear spin resonance spectroscopy as well as x-ray crystallography.

Metalloprotein Design and Engineering

Metalloproteins help catalyze some of the most difficult biological reactions and fine-tune the reactivity at a level unmatched by non-metalloproteins using different metal ions, different redox states of the same metal ions, or different ligands or geometric arrangement of the same metal ions in the same redox state. While much progress has been made on the study of native metalloproteins, little is known about how to design a metalloprotein with desired structure and activity. By using stable, easy-to-produce, and well-characterized proteins as scaffolds, we have successfully engineered CuA and CuB-heme centers in cytochrome c oxidase, manganese peroxidase, and cytochrome P450. Our success promises to change ways biomimetic studies are carried out, and to provide an alternate method to de novo protein design.

New DNA and RNA Enzymes as Anti-viral Pharmaceutical Agents or as Metal Biosensors

Recent results have shown that DNA and RNA not only are important in genetic information transfer, but also can be enzymes that can catalyze a variety of different reactions. This discovery has lead to the development of DNA and RNA enzymes as promising pharmaceutical agents against AIDS and other retroviral diseases. To obtain new DNA and RNA enzymes with high anti-viral activity for pharmaceutical applications and with strong metal-binding affinity for biophysical studies, we have used a technique called in vitro selection to select, from a library of 1014-1015 DNA molecules with different sequences, a group of Zn(II)-dependent DNA enzymes that has one of the highest activity and metal ion affinity to date. These results open a new avenue for spectroscopic and kinetic study of catalytic metal binding sites in nucleic acid enzymes and for their pharmaceutical applications. Furthermore, we are the first to report a new application of DNA enzymes as biosensors for metal ions such as Pb2+. There is an urgent need for real-time, on-site detection of lead ions with high sensitivity and selectivity because of the adverse effects of lead ions on the health of the public in general and young children in particular. Our DNA enzyme biosensor combines the high selectivity of DNA enzymes (> 80 fold for Pb2+ over other divalent metal ions) with the high sensitivity of fluorescence detection (> 400% signal increase), and can be applied to the quantitative detection of Pb2+ over a concentration range of three orders of magnitude. The easy adaptability of DNA to optical fiber and chip technology makes this DNA enzyme system an ideal choice for simple, real-time, and remote sensing of Pb2+ in applications such as environmental monitoring, clinical toxicology, and industrial process monitoring. Finally, we are interested in the immobilization of these DNA/RNA enzymes onto the surface of different materials or into the channels of micro-fluidic device so that new generation of functional biomaterials can be obtained as either sensors or controllers.