The emergence of structural genomics, proteomics, and the large-scale sequencing of many genomes provides experimental access to regions of protein sequence-structure-function landscapes which have not been explored through traditional biochemical methods. Indeed, protein structure-function relationships can now be examined rigorously through the characterization of protein ensembles, which display structurally convergent—divergent solutions to analogous or very similar functional properties. In this modern biochemical context, my lab will use protein libraries, chemistry, biophysics, molecular biology and structural methods to examine the basis of molecular recognition in the context of several important biological problems, including structural and mechanistic aspects of multi-drug resistance, ligand-dependent molecular switches and metal ion homeostasis.
L.A. Brammer, J.M. Smith, H. Wade, C. Freel Meyers. 2011. 1-Deoxy-D-xylulose 5-phosphate synthase: A new twist in thiamine diphosphate-dependent enzymology. J. Biol. Chem. in the press, doi:10.1074/jbc.M111.259747
S. Bachas, C. Eginton, D. Gunio, H.Wade. 2011. Contributions to multidrug recognition in BmrR. PNAS 108(27) 11046-11051.
H. Wade. 2010. MD recognition by MDR gene regulators Current Opinion in Structural Biology 20(4): 489-496.
S. Hu, Z. Xie, A. Onishi, X. Yu, L. Jiang, J. Lin, H.S. Rho, C. Woodard, H. Wang, J.S. Jeong, S. Long, X. He, H. Wade, S. Blackshaw, J. Qian, and H. Zhu. 2009. Profiling the human protein-DNA interactorne reveals ERK2 as a transcriptional repressor of interferon signaling. Cell 139(3): 610-622.
H. Wade, S. Stayrook, W.F. DeGrado 2006. Diferric structure of a model diiron protein; implications for cofactor stabilization and catalysis.Angew. Chem. Int. Ed. 45(30): 4951.4954.
P.P. Wei, A.J. Skulan, H. Wade, W.F. DeGrado, E.I. Solomon 2005. Spectroscopic and computational studies of the de novo designed protein DF2t: correlation to the biferrous active site of Ribonucleotide Reductase and factors that affect O2 reactivity. Journal of the American Chemical Society 127(46): 16098-16101.
O. Maglio, F. Nastri, J. Calhoun, S. Lahr, H. Wade, V. Pavone, W.F. DeGrado, A. Lombari 2005. Artificial diiron proteins: solution characterization of four-helix bundles containing two distinct types of inter-helical loops. Journal of Biological Inorganic Chemistry 10(5): 539-49.
H. Wade, S. Stayrook, W.F. DeGrado 2006. Towards the de novo design of a catalytically active helix bundle: Geometric variability at the active-site. Submitted: Journal of the American Chemical Society .
H. Wade, S. Stayrook, W.F. DeGrado 2003. Structural analysis of a de novo designed metalloprotein. Journal of Inorganic Biochemistry 96(1): 246.
H. Wade and Thomas S. Scanlan. 2003. A thermodynamic analysis of transition-state stabilization and transition-state analog binding. ChemBioChem 4(6): 537-540.
H. Wade,* Luigi Di Costanzo,* Silvano Geremia, Lucio Randaccio, Vincenzo Pavone, William F. Grado, and Angela Lombardi. 2001. Towards the de novo design of a catalytically active helix bundle: A substrate-accessible carboxylate-bridged dinuclear metal center. Journal of the American Chemical Society 123(51):12749-12757.
*first two authors contributed equally to the work.