Ernesto Fuentes, PhD

Associate Professor of Biochemistry

Contact Information

Primary Office: 4-632 BSB
Iowa City, IA 52242


BChE, Chemical Engineering, University of Dayton
MS, Biology, University of Dayton
PhD, Biochemistry, University of Illinois

Post Doctoral Fellow, Structural Biology, University of Pennsylvania
Post Doctoral Fellow, Structural and Cancer Biology, University of North Carolina

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Molecular and Cellular Biology, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Center, Program and Institute Affiliations

Center for Biocatalysis and Bioprocessing, Holden Comprehensive Cancer Center

Research Summary

Research in my laboratory focuses on important problems in signal transduction pertinent to human health. Our approach is interdisciplinary, combining, biochemical, biophysical, cell biological and molecular biology methods to gain insight into the mechanisms governing signal transduction in eukaryotic and prokaryotic systems. The major goal is to elucidate the molecular mechanisms that regulate signal transduction. Our recent work has focused on two systems.

The first system involves the Rho family of GTPases, a subfamily of the well known Ras superfamily. In their active state, Rho GTPases interact with effector proteins to coordinate changes in gene expression and the actin cytoskeleton. Several molecules, including guanine exchange factors (GEFs), regulate the active state of Rho GTPases. Importantly, the aberrant function of GEFs has been associated with developmental anomalies, mental retardation, and human disease. The long-term goal of this research is to understand the detailed molecular mechanism(s) by which GEF proteins regulate the activation of Rho-family GTPases and how their deregulation leads to disease.

The second system centers on bacterial chemosensory in the soil bacterium Myxococcus xanthus. Chemosensory in Myxococcus xanthus is essential for developmental gene expression, biofilm formation, intercellular communication and gliding motility. In collaboration with Dr. John Kirby (U of I, Microbiology) we are elucidating the biochemical and structural basis for Myxococcus xanthus chemosensory signaling.


Liu, X., Speckhard, D. C., Shepherd, T. R., Sun, Y. J., Hengel, S. R., Yu, L., Fowler, C. A., Gakhar, L. & Fuentes, E. J. (2016). Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions. Structure (London, England : 1993), 24(12), 2053-2066. PMID: 27998539.

Darnell, C., Wilson, J., Tiwari, N., Fuentes, E. & Kirby, J. (2014). Chemosensory regulation of a HEAT-repeat protein couples aggregation and sporulation in Myxococcus xanthus. J Bacteriol, 196(17), 3160-8. PMID: 24957622.

Liu, Y., Collins, C., Kiosses, W. B., Murray, A. M., Joshi, M., Shepherd, T. R., Fuentes, E. J. & Tzima, E. (2013). A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. The Journal of cell biology, 201(6), 863-73. PMID: 23733346.

Liu, X., Shepherd, T. R., Murray, A. M., Xu, Z. & Fuentes, E. J. (2013). The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics. Structure (London, England : 1993), 21(3), 342-54. PMID: 23395182.

Joshi, M., Gakhar, L. & Fuentes, E. J. (2013). High-resolution structure of the Tiam1 PHn-CC-Ex domain. Acta crystallographica. Section F, Structural biology and crystallization communications, 69(Pt 7), 744-52. PMID: 23832200.

Willett, J. W., Tiwari, N., Muller, S., Hummels, K. R., Houtman, J. C., Fuentes, E. J. & Kirby, J. R. (2013). Specificity residues determine binding affinity for two-component signal transduction systems. MBio, 4(6), e00420-13. PMID: 24194534.

Shepherd, T. R., Fuentes, E. J. (2011). Structural and thermodynamic analysis of PDZ-ligand interactions. Methods in enzymology, 488, 81-100. PMID: 21195225.

Shepherd, T. R., Hard, R. L., Murray, A. M., Pei, D. & Fuentes, E. J. (2011). Distinct ligand specificity of the Tiam1 and Tiam2 PDZ domains. Biochemistry, 50(8), 1296-308. PMID: 21192692.

Wen, H., Kim, N., Fuentes, E. J., Mallinger, A., Gonzalez-Alegre, P. & Glenn, K. A. (2010). FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest. Cell cycle (Georgetown, Tex.), 9(22), 4506-17. PMID: 21135578.

Shepherd, T. R., Klaus, S. M., Liu, X., Ramaswamy, S., DeMali, K. A. & Fuentes, E. J. (2010). The Tiam1 PDZ domain couples to Syndecan1 and promotes cell-matrix adhesion. Journal of molecular biology, 398(5), 730-46. PMID: 20361982.

Ramadugu, S. K., Chung, Y. H., Fuentes, E. J., Rice, K. G. & Margulis, C. J. (2010). In silico prediction of the 3D structure of trimeric asialoglycoprotein receptor bound to triantennary oligosaccharide. Journal of the American Chemical Society, 132(26), 9087-95. PMID: 20540518.

Law, A. B., Fuentes, E. J. & Lee, A. L. (2009). Conservation of side-chain dynamics within a protein family. Journal of the American Chemical Society, 131(18), 6322-3. PMID: 19374353.

Petit, C. M., Zhang, J., Sapienza, P. J., Fuentes, E. J. & Lee, A. L. (2009). Hidden dynamic allostery in a PDZ domain. Proceedings of the National Academy of Sciences of the United States of America, 106(43), 18249-54. PMID: 19828436.

Fuentes, E. J., Gilmore, S. A., Mauldin, R. V. & Lee, A. L. (2006). Evaluation of energetic and dynamic coupling networks in a PDZ domain protein. Journal of molecular biology, 364(3), 337-51. PMID: 17011581.

Tsonis, P. A., Fuentes, E. J. (2006). Focus on molecules: Pax-6, the eye master. Experimental eye research, 83(2), 233-4. PMID: 16563385.

Fuentes, E. J., Der, C. J. & Lee, A. L. (2004). Ligand-dependent dynamics and intramolecular signaling in a PDZ domain. Journal of molecular biology, 335(4), 1105-15. PMID: 14698303.

Fuentes, E. J., Karnoub, A. E., Booden, M. A., Der, C. J. & Campbell, S. L. (2003). Critical role of the pleckstrin homology domain in Dbs signaling and growth regulation. The Journal of biological chemistry, 278(23), 21188-96. PMID: 12637530.

Kranz, J. K., Flynn, P. F., Fuentes, E. J. & Wand, A. J. (2002). Dissection of the pathway of molecular recognition by calmodulin. Biochemistry, 41(8), 2599-608. PMID: 11851407.

Dai, Q. H., Tommos, C., Fuentes, E. J., Blomberg, M. R., Dutton, P. L. & Wand, A. J. (2002). Structure of a de novo designed protein model of radical enzymes. Journal of the American Chemical Society, 124(37), 10952-3. PMID: 12224922.

Liu, W., Flynn, P. F., Fuentes, E. J., Kranz, J. K., McCormick, M. & Wand, A. J. (2001). Main chain and side chain dynamics of oxidized flavodoxin from Cyanobacterium anabaena. Biochemistry, 40(49), 14744-53. PMID: 11732893.

Gibney, B. R., Huang, S. S., Skalicky, J. J., Fuentes, E. J., Wand, A. J. & Dutton, P. L. (2001). Hydrophobic modulation of heme properties in heme protein maquettes. Biochemistry, 40(35), 10550-61. PMID: 11523997.

Fuentes, E. J., Wand, A. J. (1998). Local dynamics and stability of apocytochrome b562 examined by hydrogen exchange. Biochemistry, 37(11), 3687-98. PMID: 9521687.

Fuentes, E. J., Wand, A. J. (1998). Local stability and dynamics of apocytochrome b562 examined by the dependence of hydrogen exchange on hydrostatic pressure. Biochemistry, 37(28), 9877-83. PMID: 9665691.

Qi, P. X., Fuentes, E. J., Beckman, R. A., Di Stefano, D. L. & Wand, A. J. (1995). Solution Structures of horse ferro- and ferricytochrome c using 2D and 3D 1H NMR and restrained simulated annealing. J. W. Crab (Eds.) pp. 511-519. Techniques in Protein Chemistry VI.

Fuentes, E. J., Pachter, R. & Tsonis, P. A. (1994). On the three-dimensional structure of the Hydra head activator neuropeptide. In vivo (Athens, Greece), 8(2), 199-205. PMID: 7919122.

Qi, P. X., Urbauer, J. L., Fuentes, E. J., Leopold, M. F. & Wand, A. J. (1994). Structural water in oxidized and reduced horse heart cytochrome c. Nature structural biology, 1(6), 378-82. PMID: 7664051.

Fuentes, E. J., Mescher, A. L., Ekman, R. & Tsonis, P. A. (1993). Expression of hydra head activator in newt tissues and effects on limb regeneration. In vivo (Athens, Greece), 7(1), 59-63. PMID: 8389215.