My research focuses on determining structural and functional relationships involving proteins and small-molecules (organic and inorganic compounds). I use a variety of different physical and computational techniques to determine functional relationships, including: Crystallography, Enzymology, Protein-Protein computational docking, Protein-ligand docking, and bioinformatics. Some of my current research projects are listed below:

The CREC Protein Family

The CREC Protein Family is a recently discovered protein family with similar sequences but unknown functions. The CREC protein family consists of a number of low-affinity calcium binding proteins containing multiple EF-hand Ca2+ binding motifs. The CREC proteins are found throughout the secretory pathway of mammals and invertebrates, but their exact function and structure are still unknown. These proteins have been shown to interact with a number of other proteins, and have been associated with a number of disease states, including cancer, malaria, and toxin mediation. Knowledge about the function and structure of the CREC proteins will provide further insights into protein trafficking and cancer invasiveness

Aminoglycoside 6'-acetyltransferase Type Ib (AAC-6')

AAC-6’ is an enzyme with confers antibiotic resistance by catalyzing the acetylation of Kanamycin and Gentimycin. The AAC-6’ gene was initially found in a novel transposon in clinical strains of K. pneumonia. Since then, the gene has been found in other pathogenic organisms. The enzyme mechanism is known but the active pocket and the catalytic residues have not yet been identified. Identification of the active pocket and the catalytic residues will help us find potential inhibitors for this enzyme.

Prediction of the catalytic residues.

Genomic research is producing gene sequences at a record pace, but the functions of many of these genes are unknown. The NIH has initiated the structural genomics project in an attempt to use structural homology to identify the function of the genes where sequence homology has failed or proved inconclusive. Recently, a number of methods for predicting the catalytic residues of a protein have been suggested. Most of these methods rely heavily on sequence homology to identify the active pocket and the catalytic residues. Sequence homology methods tend to miss-identify about 1/3 of the catalytic residues, because these residues are not conserved. Sequence homology methods also tend to have a high number of false positives that need to be filtered out. A number of structure based methods have also appeared. The structure based methods are typically used in conjunction with a sequence based method to help filter out the false positives. One of the short comings of this field is the lack of known enzymes with both structural and catalytic information. While the active pockets and catalytic residues of a large number of enzymes have been reported in the literature, there is no standardized database which contains the catalytic residues. My lab will focus on two specific areas of catalytic residue prediction. First we will create a large database which lists enzymes by their EC number and contains the active pocket location, the catalytic residues, the pH profile, and the effects of any known mutation on the activity of the enzyme. Second we want to test the previously published methods using a standardized test set of enzymes generated from our extensive database and then try to improve the existing predictive methods and to identify new potential methods.