The main goals of my research program are to understand the structure/function relationship of key biomacromolecules and apply the acquired structural information in drug development. Using X-ray crystallography/cryo-EM in conjunction with various complementary biochemical/biophysical approaches, my laboratory have successfully determined dozens of high-resolution crystal structures of proteins and protein-DNA complexes over the past few years. Key results include the structures of human type IIA topoisomerases in complexes with DNA and anticancer drugs, the DNA-wrapping domains of bacterial type IIA topoisomerases, the MerR dual-function transcriptional regulator with an unique DNA-twisting activity, and enzymes involved in crucial biosynthetic pathways or of prominent clinically relevance (such as human ornithine decarboxylase, phosphodiesterases, methyltransferases, and members of the α-ketoglutarate-dependent non-heme iron-containing enzyme superfamily). The structures of type IIA topoisomerases and MerR transcriptional regulator have provided new insights into how topological and conformational changes of DNA may be regulated. And the structures of various enzymes we determined have elucidated the molecular bases underlying the catalytic and inhibitory mechanisms of the respective enzymes.
