Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology; Professor of Chemistry
The overall goal of the research in our laboratory is to relate the three-dimensional structure and dynamics of proteins to their biological functions. We use techniques of X-ray crystallography and other biophysical methods to elucidate the molecular structures, dynamics, and functions of proteins. Extensive use is made of modern computational methods to analyze the structures and their dynamics.
One project we have underway is directed towards obtaining an atomic description of the basis for binding of oxygen and other ligands to heme proteins. Detailed three-dimensional structures are being determined for modified myoglobins and hemoglobins and other novel heme proteins, such as nitrobindin, a protein we discovered that reversibly binds nitric oxide and is found throughout the animal kingdom.. We are also working to develop new techniques for observing the dynamics of proteins and nucleic acids using diffuse X-ray scattering analysis and molecular dynamics simulations. The result will be a transition from "snapshots" of macromolecules to the generation of "movies" of molecules in action.
Organisms have proteins that are highly adapted to the growing conditions in the environment. We have determined structures of enzymes from hyperthermophilic bacteria to reveal aspects of the connections of protein structure to dynamics, which is an integral part of proteins' designs. We have also developed new methods of improving the thermostability of proteins for potential commercial improvements.
Members of the laboratory are also involved in the field of structural genomics, the solving of structures whose function may not yet be known. The structures often give clues about the functions. We are currently working on structures of enzymes involved in natural product biosynthesis in order to help produce lead compounds for cancer pharmaceutical discovery. More recently, members of my laboratory have become involved in the Great Lakes Bioenergy Research Center, whose mission is to contribute basic science results to the development of biofuel, particularly cellulosic ethanol.
A longstanding interest in the laboratory is also computational biology. This activity entails the development and application of modern algorithms from computer science and applied mathematics to solve interesting biological problems.
Research and Teaching Links
Burgie, S.E., Walker, J.M., Phillips, G.N., Jr, Vierstra, R.D. A unique photo-labile thioether linkage in the DXCF-family of cyanobateriochromes provides the structural basis for their blue/green photocycles. Structure 2012
Bryden Aaron; Phillips George N. Jr.; Gleicher Michael. Automated Illustration of Molecular Flexibility. IEEE Transactions On Visualization And Computer Graphics , 18 2012: 132-145
Bitto, E., Kim, D.J., Bingman, C.J., Kim, H.-J., Han, B.W., Phillips, G.N., Jr. Crystal structure of tandem ACT domain-containing protein ACTP from Galdieria sulphuraria. Proteins, 80 2012: 2105-09
Bailey, L.J., Acheson, J.F., McCoy, J.G., Elsen, N.L., Phillips, G.N., Jr, Fox, B.G. Crystallographic analysis of active site contributions to regiospecificity in the diiron enzyme toluene-4-monooxygenase. Biochemistry , 51 2012: 1101-1113
Daily, M.D., Phillips, G.N, Jr. and Cui, Q. Large-scale motions in the adenylate kinase solution ensemble: coarse-grained simulations and comparison with solution x-ray scattering . Chem. Phys. , 396 2012: 84-91
Ragsdale SW, Yi L, Bender G, Gupta N, Kung Y, Yan L, Stich TA, Doukov T, Leichert L, Jenkins PM, Bianchetti CM, George SJ, Cramer SP, Britt RD, Jakob U, Martens JR, Phillips GN, Drennan CL. Redox, haem and CO in enzymatic catalysis and regulation. Biochem. Soc. Trans. , 40 2012: 501-507
Bianchetti, C.M., Smith, R.W., Rutkoski, T.J., Brumm, P., Phillips, G.N., Jr. Structure and mechanism of Endoglucanase D from Clostridium cellulovorans . 2012
Singh, S., Phillips, G.N., Jr., Thorson, J.S. The structural biology of enzymes involved in natural product glycosylation. Natural Products Reports , 29 2012: 1201-37
Chang, A., Singh, S., Phillips, G.N., Jr. Thorson, J.S. Glycotransferase structural biology and its role in the design of catalysts for glycosylation. Current Opinion in Biotechnology 2011, in press
Daily, M.D., Phillips, G.N, Jr. and Cui, Q. Large-scale motions in the adenylate kinase solution ensemble: coarse-grained simulations and comparison with solution x-ray scattering. Chem. Phys. 2011, in press
Singh, S., Chang, A., Goff, R., Bingman, C.A., Gruschow, S., Sherman, D.A., Phillips, G.N., Jr., Thorson, J. Structural characterization of the mitomycin 7-O-methyltransferase, MmcR. . Proteins 2011, in press
Gonzales-Vigil, E., Bianchetti, C.M., Phillips, G.N., Jr., and Howe, G.A. Adaptive evolution of threonine deaminase in plant defense against insect herbivores. Proc. Natl. Acad. Sci. , 108 2011: 5897-5902
Chang, A., Singh, S., Helmich, K.E., Goff, R.D., Bingman, C.A., Thorson, J.S., Phillips, G.N., Jr. Complete set of glycosyltransferase structures in the calicheamicin biosynthetic pathway reveals the origin of regiospecificity. Proc Natl Acad Sci USA , 108 2011: 17649-54
Han, B.W., Malone, T.E., Kim, D.J., Bingman, C.A., Kim, H.-J., Fox, B.G., Phillips, G.N., Jr. Crystal structure of Arabidopsis thaliana 12-oxophytodienoate reductase isoform 3 in complex with 8-iso prostaglandin A1. Proteins, 79 2011: 3236-41
Bianchetti, C.M., Elsen, N.L., Fox, B.G., Phillips, G.N., Jr. Crystal structure of cellobiose phosphorylase from Clostridium thermocellum in complex with phosphate. Acta Crystallographica F 2011
Moretti, R., Chang, A., Peltier-Pain, P., Bingman, C.A., Phillips, G.N., Jr. Thorson, JS. Expanding the nucleotide and sugar-1-phosphate promiscuity of nucleotidyltransferase RmlA via directed evolution. J. Biol. Chem. , 286 2011: 13235-13243
Daily, M.D., Phillips, G.N., Jr., Cui, Q. Interconversion of functional motions between mesophilic and thermophilic adenylate kinases. PLoS Computational Biology , 7 2011
Chundawat, S.P.S., Bellesia, G., Sousa, L., Gao, D., Cheh, A., Agarwal, U., Bianchetti, C.M., Phillips, G.N., Jr., Langan. P., Balan, V., Gnanakaran, S., Dale, B. Restructuring crystalline cellulose hydrogen bond network enhances its depolymerization rate. JACS, 133 2011: 11163-74
Burgie E.S., Bingman, C.A., Phillips, G.N., Jr. Structural architecture of Galdieria sulphuraria DCN1L. Proteins, 79 2011: 1329-1336
Chang, A., Singh, S., Bingman, C.A., Thorson, J.S. and Phillips, G.N., Jr. Structural characterization of CalO1: a putative orsellinic acid methyltransferase in the calicheamicin biosynthetic pathway. Acta Cyrst D , 67 2011: 197-203
Burgie E.S., Bingman, C.A., Grundhoefer, S.L., Soni, A., Phillips, G.N., Jr. Structural characterization of Uch37 reveals the basis of its auto-inhibitory mechanism. Proteins 2011
Bianchetti, C.A., Bingman, C.A., and Phillips, G.N., Jr. Structure of the C-terminal Heme-binding domain of THAP-domain-containing protein 4 from Homo sapiens. Proteins, 79 2011: 1337-1341