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Elias Fernandez F435 Walters Life Sciences |
Keywords:
X-ray crystallography, signal transduction, nuclear receptor, transcription, G protein, pharmacology
Description of Research:
My research interests are concerned with the three-dimensional structures of proteins and the relevance of these structures in biology. The laboratory utilizes the techniques of X-ray crystallography for protein structure determination, molecular biology for heterologous over-expression and site-directed mutagenesis, and protein biochemistry, cell biology and computational Molecular Dynamics simulations for quantification of biomolecular interactions. These methods are applied to several biological problems that include the molecular basis of signal transduction, the mechanism of hormone action, and the assembly and gating of ion channels.
Proteins of interest to my laboratory belong to several classes such as G proteins, non-receptor tyrosine kinases and their protein trans-inhibitors, nuclear hormone receptors, ion channels and proteins that assist in DNA repair. All these proteins are associated with critical biological processes and have been linked to diverse clinical conditions. Thus, molecular insight into the functioning of these molecules will have broad therapeutic applications.
We have recently determined the structure of the ligand binding domain of the constitutive androstane receptor (CAR), a protein belonging to the nuclear receptor superfamily. This is the first novel protein structure from UT Knoxville. We have also crystallized a novel NAD/NADH+ kinase.
Selected Publications:
- Vincent J, Shan L, Fan M, Brunzelle JS, Forman BM and Fernandez E (2005) Crystallographic analysis of murine constitutive androstane receptor ligand-binding domain complexed with 5alpha-androst-16-en-3alpha-ol. Acta Cryst. F61:156-159.
- Shan L, Vincent J, Brunzelle JS, Dussault I, Lin M, Ianculescu I, Sherman MA, Forman BM and Fernandez EJ (2004) Structure of the murine constitutive androstane receptor complexed to androstenol; a molecular basis for inverse agonism. Molecular Cell. Dec 22; 16(6):907-17.
- Fernandez EJ and Lolis E (2002) Structure, Function, and Inhibition of Chemokines Annu. Rev. Pharmacol. Toxicol. 42: 469-99.
- Fernandez EJ, Wilken J, Thompson D, Peiper S and Lolis E (2000) Comparison of the Structure of vMIP-II with Eotaxin-1, RANTES, and MCP-3 Suggests a Unique Mechanism for CCR3 Activation Biochemistry 39: 12837-12844.
- *Dealwis C, *Fernandez EJ, Thompson DA, Simon RJ, Siani MA and Lolis E (1998) Crystal structure of chemically synthesized [N33A] stromal cell-derived factor-1a, a potent ligand for the HIV-1 ‘fusin’ coreceptor. Proc. Natl. Acad. Sci. USA 95:6941-6946. * Joint first authors.
- Fernandez EJ, Abad-Zapatero C and Olsen, KW (2000) Crystal structure of Lysb182 – Lysb282 Crosslinked Hemoglobin: A possible Allosteric Intermediate. J. Mol. Biol. 296(5): 1263-1274.
- Fernandez E, Johemiack A and Lolis E (2000) A cryo-cooling technique for proteins grown from volatile solvents. J. App. Cryst. 33: 168-171.