【报告题目】 Biochemistry and Structural Biology of Selenium and Tellurium Nucleic Acids
Department of Chemistry & Department of Biology, Georgia State University, Atlanta, GA 30303, USA;
3D structure studies of nucleic acids provide novel insights into nucleic acid molecules. As oxygen, selenium and tellurium are in the same elemental family, the atom-specific replacement by replacing nucleotide oxygen with selenium or tellurium has revealed novel chemistry, structure, function and mechanism of nucleic acids. The Se and Te derivatizations lead to a novel paradigm of nucleic acids and allow discoveries of new applications and materials, such as self-assembling nano-electronic materials and sensors. Furthermore, X-ray crystallography is a powerful tool for structure determination of DNA and RNA structures, RNA-protein and DNA-protein complexes with high resolution. However, besides crystallization problem, derivatization with heavy atoms for phase determination has largely slowed down structural determination of nucleic acids with novel structures and folds. Our nucleic acid chemogenetic strategy with selenium has demonstrated great potentials as a general methodology for structure and function studies of nucleic acids as well as their protein complexes. Furthermore, we find that the Se-derivatized nucleic acids have virtually identical structures to the corresponding natives, while the conventional Br-derivatization caused severe perturbations on the local backbone and hydration. Furthermore, we found that the Se-derivatization can facilitate crystallization and the diffraction quality is high. Our results suggest that the Se derivatization is a better alternative to the conventional Br derivatization. This Se derivatization strategy via the atom-specific substitution will significantly facilitate crystal structure studies of nucleic acids as well as their protein complexes. Excitingly, we have recently determined the first nucleic acid-protein complex via the nucleic acid Se-derivatization and the MAD phasing.
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