The overall goal of our laboratory is to characterize the structure/function relationships of a variety of enzymatic catalysts at the atomic level. Much of this work is being extended into efforts to engineer novel structures and properties onto existing protein and enzyme scaffolds. A unifying theme between many of the individual projects is the selection and engineering of these enzymes for targeted therapeutic and/or biotech/industrical applications.
The tools employed by our lab are X-ray crystallography, computer modeling, and genetic manipulation of the molecules of interest, combined with biochemical analyses of function.
Forsberg KJ, Bhatt IV, Schmidtke DT, Javanmardi K, Dillard KE, Stoddard BL, Finkelstein IJ, Kaiser BK, Malik HS (2019) “Functional metagenomics-guided discovery of potent Cas9 inhibitors in the human microbiome” eLife Sep 10;8. pii: e46540. doi: 10.7554/eLife.46540. PMID 31502535.
Shen, B.W., Doyle, L., Bradley, P., Heiter, D.F., Lunnen, K.D. Wilson, G. G., and Stoddard, B.L. (2019) "Structure, subunit organization and behavior of the asymmetric Type IIT restriction endonuclease BbvCI" Nucleic Acids Research 47(1):450-467 . doi: 10.1093/nar/gky1059. PMID 3035313.
Day AL, Greisen P, Doyle L, Schena A, Stella N, Johnsson K, Baker D, Stoddard B. (2018) "Unintended specificity of an engineered ligand-binding protein facilitated by unpredicted plasticity of the protein fold" Protein Engineering 31(10):375-387. doi: 10.1093/protein/gzy031 PMID 30566669.