The overall objective of this project is to continue investigating the conformational diversities of nucleic acids using x-ray crystallography and nuclear magnetic resonance spectroscopy. Other biophysical techniques, such as laser Raman and circular dichroism spectroscopic methods, will be applied when necessary. Several molecular systems, containing carefully-designed DNA/RNA oligonucleotide sequences associated with important biological implications, will be studied and their structures correlated with biological functions. We propose to study the following DNA/RNA systems for various objectives. (i). Unusual nucleic acid con formations: Several new unusual nucleic acid conformations (e.g., Z-DNA, H-DNA, I-DNA, Hoogsteen helix, telomere, centromere) have been uncovered recently. We will continue to study the molecular basis of those structures and to explore new and unusual conformations. (ii). Nucleic acid structure with defects. Oligonucleotides with different kinds of irregular features such as mismatch, bulge and carcinogen-modified base (e.g., m6G/m4T, benzopyrene-adduct) will be studied. Different modified nucleotide analogs will be incorporated into double helix to assess the effect of them on the stability of various alternative DNA/RNA conformations. (iii). Higher-ordered structures. Nucleic acid molecules can form quite complex tertiary structures like triple helix, hairpin, cruciform, pseudoknot and circular molecules, all of which are important in biological processes (e.g., in gene regulation and recombination). We will continue to focus on the structures of hairpins and circular DNA. (iv). Ligand-nucleic acid interactions. The function of nucleic acids depends on their interactions with other molecules. We will study the interactions between a number of small ligands (in particular metal ions) and nucleic acids by x-ray crystallography. We will explore the crystallization of a few non-sequence-specific DNA binding proteins (e.g., M13 gene V protein and HU) and their DNA complexes. A significant number of those molecules described above are already in various stages of structural analysis. New molecules in the above scope will be synthesized and studied structurally by x-ray diffraction and NMR. The detailed descriptions of various molecular systems are listed in the Preliminary Results section. Our studies will help understand the molecular forces that governs the structure, dynamics and energetics of nucleic acids.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Physical Biochemistry Study Section (PB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
Zip Code
Ko, T P; Chen, Y K; Robinson, H et al. (2001) Mechanism of product chain length determination and the role of a flexible loop in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis. J Biol Chem 276:47474-82
Su, S; Gao, Y G; Robinson, H et al. (2000) Crystal structures of the chromosomal proteins Sso7d/Sac7d bound to DNA containing T-G mismatched base-pairs. J Mol Biol 303:395-403
Robinson, H; Gao, Y G; Sanishvili, R et al. (2000) Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes. Nucleic Acids Res 28:1760-6
Hakansson, K; Broder, D; Wang, A H et al. (2000) Crystallization of peptidase T from Salmonella typhimurium. Acta Crystallogr D Biol Crystallogr 56:924-6
Gao, Y G; Robinson, H; Sanishvili, R et al. (1999) Structure and recognition of sheared tandem G x A base pairs associated with human centromere DNA sequence at atomic resolution. Biochemistry 38:16452-60
Robinson, H; Ang, M C; Gao, Y G et al. (1999) Structural basis of electron transfer modulation in the purple CuA center. Biochemistry 38:5677-83
Gao, Y G; Robinson, H; Guan, Y et al. (1998) Molecular structure of two crystal forms of cyclic triadenylic acid at 1A resolution. J Biomol Struct Dyn 16:69-76
Guan, Y; Benevides, J M; Gao, Y G et al. (1998) Structural polymorphism and raman conformation markers of cyclic deoxytriadenylic acid. Nucleic Acids Res 26:3892-99
Yang, X L; Sugiyama, H; Ikeda, S et al. (1998) Structural studies of a stable parallel-stranded DNA duplex incorporating isoguanine:cytosine and isocytosine:guanine basepairs by nuclear magnetic resonance spectroscopy. Biophys J 75:1163-71
Robinson, H; Gao, Y G; Bauer, C et al. (1998) 2'-Deoxyisoguanosine adopts more than one tautomer to form base pairs with thymidine observed by high-resolution crystal structure analysis. Biochemistry 37:10897-905

Showing the most recent 10 out of 48 publications