Clark Lab

Department of Biology
University of Texas at Arlington

Macromolecular x-ray crystallography is a means of determining the 3-dimensional structure of a macromolecule from the systematic scattering of x-rays by a crystal made of that macromolecule. Biological macromolecules include protein, DNA, RNA, and combinations of the three. Purified biological molecules are used to grow a crystal that is then collected and prepared for analysis. The crystal is positioned in the x-ray beam and diffracted, and x-rays are detected using an image plate detector. Data analysis and processing followed by modeling of the data yield the 3-dimensional structure. The structural models are used to provide information on the function of the macromolecules as well as to understand how changes in the macromolecules are important in disease states.

We use x-ray crystallography to study the relationship between the structure of caspases and their function. In particular, we are interested in how cells regulate the conformations of caspases in order to fine-tune caspase activity during cell death (apoptosis) and differentiation. In addition, we use the 3-dimensional models of caspases to guide the design of small drug compounds that affect caspase function.

This link to the protein data bank (PDB) lists the caspase structures determined by the Clark lab.

 

 

 

 

 

 

 

 

 

 

Keywords

Allostery, Apoptosis, Caspases, Cancer Biology, Protein Engineering, X-ray Crystallography, Spectroscopy (Equilibrium and Kinetic Studies), Isother mal Titration Calorimetry, Analytical Ultracentrifugation, Molecular Modeling, Molecular Dynamics, Site-Directed Mutagenesis, Assay Development, Transfection, Western Analysis, RT-PCR, Cell Sorting, Transgenic Animals, Phage Display