Protein Crystallography

Our laboratory is interested in the relationship of macromolecule three-dimensional structures to biochemical functions. The tools employed are X-ray crystallography, molecular biology, and protein chemistry.

The first research area focuses on enzymatic mechanisms, and mechanisms of protein autoproteolysis and splicing which are posttranslational processing events. We are pursuing structural studies of the autoproteolysis mechanism of glycosylasparaginase, whose mutations in humans result in an inherited lysosomal storage disorder aspartylglycosaminuria (AGU), and the autoproteolysis of a nucleoporin, Nup98, that plays important roles in the nucleocytoplasmic transport of proteins and RNAs.

The second research area is to study enzymes involved in antigen presentation. For an epitope to be recognized by T cells, foreign antigens need to be cut into short peptides with proper sizes in order to form physical complexes with MHC molecules. A few aminopeptidases have recently been identified to play critical roles in trimming peptide precursors and generating the final N-termini of class I-restricted epitopes. We are pursuing structural studies on these critical enzymes.

The other research areas are structural studies of factors interacting with nucleic acids. These include transcription factors, regulatory proteins, reverse transcriptases, as well as restriction enzymes with unique DNA cleavage patterns. The goal is to understand the structural basis for their functions, and specific interactions of protein-protein and protein-nucleic acid, at atomic resolution.