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George Phillips

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.Phillips Research

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

Publications

Auldridge, M.E., Cao, H., Sen, S., Franz., L.P., Bingman, C.A., Yennamalli, R.M., Phillips, G.N., Jr., Mead, D., Steinmetz, E.J., LucY: a versatile new fluorescent reporter protein. PLOS One 10:e0124272 (2015). PMCID:PMC4408115

Samuel, Premila P., Smith, L.P., Phillips, G.N., Jr. Olson, J.S., Apoglobin stability is the major factor governing both cell-free and in vivo expression of holoMb,  J. Biol. Chem. 290(39):23479-95 (2015) PMCID: PMC4583012 

Park, M.S., Bitto, B., Bingman, C.A., Kim, K.R., Miller, M.D., Kim, H.-J., Han, B.W., Phillips, G.N., Jr. Crystal structure of human protein N-terminal glutamine amidohydrolase, an initial component of the N-end rule pathway. PLoS One 9:e111142 (2014) PMCID:PMC4214742

Kim, D.J., Bitto, E., Bingman, C.A., Kim, H.-J., Han, B.Y., Phillips, G.N., Jr. Crystal structure of the protein At3g01520, a eukaryotic universal stress protein-like protein from Arabidopsis thaliana in complex with AMP, Proteins83(7):1368-73  (2015) PMCID: PMC4624624 [Available on 2016-07-01] 

Rudolf, J.D., Bigelow, L., Chang, C., Cuff, M.E., Lohman, J.R., Chang, C.-Y., Ma, M., Yang, D., Clancy, S., Babnigg, G., Joachimiak, A., Phillips, G.N., Jr., Shen, B., Crystal structure of the zorbamycin-binding protein ZbmA, the primary self-resistance element in Streptomyces flavoviridis ATCC21892, Biochemistry 54(45):6842-51 (2015) PMID:26512730

Aceti, D.J., Bingman, C.A., Wrobel, R.L., Ferderick, R.O., Makino, S., Nichols, K.W., Sahu, S.C., Bergeman, L.F., Blommel, P.G., Cornilescu, C.C., Gromek, K.A., Hwang, S., Primm, J.G., Sabat, G., Vojtik, F.C., Volkman, B.F., Zolnai, Z., Phillips, G.N., Jr., Markley, J.L., Fox, B.G., Expression platforms for producing eukaryotic proteins: a comparison of E. coli cell-based and wheat germ cell-free synthesis, affinity and solubility tags, and cloning strategies.  J Struct Funct Genomics. 16:67-80 (2015) PMCID: PMC4430420 [Available on 2016-06-01] 

Huber, T.D., Wang, F., Singh, S., Johnson, B.B., Zhang, J., Sunkara, M., Van Lanen, S.G., Morris, A.J., Thorson, J.S., Functional AdoMet isosteres resistant to classical AdoMet degradation pathways (submitted)

Bryden, A., Phillips, G.N., Jr., Griguer, Y., Moxon, J., and Gleicher, M. Improving collaboration visualization of structural biology.  International Symposium on Visual Computing

Abbamonte, P. et al. New Science Opportunities Enabled by LCLS-II X-ray Lasers, Stanford Linear Accelerator Laboratory, SLAC-R-1053, May, 2015

Wang, F., Singh, S., Xu, W., Helmich, K.E., Miller, M.D., Cao, H., Bingman, C.A., Thorson, J.S., Phillips, G.N., Jr., Structural basis for the stereochemical control of amine installation in nucleotide sugar aminotransferases ACS Chemical Biology 10(9):2048-56.  (2015) PMCID: PMC4575645 [Available on 2016-09-18] 

Lohman, J.R., Ma, M., Osipiuk, J., Nocek, B., Kim, Y., Changsoo, C., Cuff, M., Mack J., Bigelow, L., Li, H., Endres, M, Babnigg, G., Joachimiak, J., Phillips, G.N., Jr., and Shen, B. Structural and evolutionary relationships of “AT-less” type I polyketide synthase ketosynthases. PNAS 112:12693-12698 (2015). PMCID: PMC4611616 [Available on 2016-04-13]

Helmich KE, Pereira JH, Gall DL, Heins RA, McAndrew RP, Bingman CA, Deng K, Holland KC, Noguera DR, Simmons BA, Sale KL, Ralph J, Donohue TJ, Adams PD, Phillips GN Jr. Structural basis of stereospecificity in the bacterial enzymatic cleavage of β-aryl ether bonds in lignin. J Biol Chem.  pii: jbc.M115.694307. [Epub ahead of print] (2015)

 Singh, S., Kim, Y., Wang, F., Bigelow, L., Endres, M., Kharel, M.K., Babnigg, G., Bingman ,C.A., Joachimiak, A., Thorson, J.S., Phillips, G.N., Jr., Structural characterization of AtmS13, a putative sugar aminotransferase involved in indolocarbazole AT2433 aminopentose biosynthesis Proteins. 2015; 83(8):1547-54 (2015) PMCID: PMC4570032 

Singh, S., Michalska, K., Bigelow, L., Endres, M., Kharel, M.K., Babnigg, G., Ragothaman, Y.A., Bingman, C.A., Joachimiak, A., Thorson, J.S., Phillips, G.N., Jr. Structural characterization of CalS8, a TDP-α-D-glucose dehydrogenase involved in calicheamicin aminodideoxypentose biosynthesis, J. Biol. Chem. 290:26249-26258 (2015) PMCID: PMC4646273 

Lu, H., Wang, F., Phillips, G.N. Jr. Structural dynamics of CalS11 methyltransferase using crystallographic ensemble refinements. (in preparation)

Yennamalli, R.M., Tan, K., Bigelow, L., Jedrzejczak, R., Babmigg, G., Bingman, C.A., Joachimiak, A., Kharel, M.K., Singh, S., Thorson, J., Phillips, G.N., Jr. Structural dynamics study of a methionine gamma-synthase involved in calicheamicin biosynthesis (in preparation)

Lohman, J.R., Ma, M., Cuff, M.D., Bigelow, L., Bearden, J., Babnigg, G., Joachemiak, A., Phillips, G.N., Jr. and Shen, B. The crystal structure of BlmI as a model for nonribosomal peptide synthetase peptidyl carrier proteins.  Proteins

Traeger, L.L., Volkening, J.D., Gallant, J.R., Moffett, H., Chen, P.-H., Novina, C.D., Phillips, G.N., Jr., Anand, R., Wells, G.B., Pinch, M., Guth, G., Unquez, G.A., Albert, J.S., Zakon, P.S., Sussman, M.R. , H.H., Manoj. Unique patterns of protein sequence evolution and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus) BMC Genomics 16:243 (2015) PMCID:PMC4393597

Bae, E., Moon, S., Phillips, G.N., Jr., Molecular dynamics simulation of a psychrophilic adenylate kinase, J. Korean Society for Appl. Biol. Chem. 58:209-212 (2015).

Weerth, R.S., Michalska, K., Bingman, C.A,. Yennamalli, R.M., Li, H., Jedrzejczak, R., Wang, F., Babnigg, G., Joachemiak, A., Thomas, M.G., Phillips, G.N., Jr., Structure of a cupin protein from photorhabdus luminescens subsp. laumondii tt01 at 1.4 Å resolution, Proteins 83:383-388 (2015). PMCID:PMC4300268

KK Desai, CL Cheng, CA Bingman, GN Phillips, RT Raines A tRNA splicing operon: archease endows RtcB with dual GTP/ATP cofactor specificity and accelerates RNA ligation.  Nucleic acids research, 42 (6) 2014: 3931-3942

S Moon, D Jung, GN Phillips, E Bae An integrated approach for thermal stabilization of a mesophilic adenylate kinase.  Proteins: Structure, Function, and Bioinformatics, 82 (9) 2014: 1947-1959

Saeid Karkehabadi, Kate E Helmich, Thijs Kaper, Henrik Hansson, Nils-Egil Mikkelsen, Mikael Gudmundsson, Kathleen Piens, Meredith Fujdala, Goutami Banerjee, John S Scott-Craig, Jonathan D Walton, George N Phillips, Mats Sandgren Biochemical Characterization and Crystal Structures of a Fungal Family 3 β-Glucosidase, Cel3A from Hypocrea jecorina.  Journal of Biological Chemistry, 289(45) 2014: 31624-31637

Mi Seul Park, Eduard Bitto, Kyung Rok Kim, Craig A Bingman, Mitchell D Miller, Hyun-Jung Kim, Byung Woo Han, George N Phillips Jr Crystal Structure of Human Protein N-Terminal Glutamine Amidohydrolase, an Initial Component of the N-End Rule Pathway.  PLoS One, 9 (10) 2014: e111142

S Moon, RM Bannen, TJ Rutkoski, GN Phillips, E Bae Effectiveness and limitations of local structural entropy optimization in the thermal stabilization of mesophilic and thermophilic adenylate kinases.  Proteins: Structure, Function, and Bioinformatics, 82 (10) 2014: 2631-2642

AJ Book, RM Yennamalli, TE Takasuka, CR Currie, GNP Jr, BG Fox Evolution of substrate specificity in bacterial AA10 lytic polysaccharide monooxygenases.  NMR, 1 (1) 2014: 17-19

JE Lomax, CM Bianchetti, A Chang, GN Phillips, BG Fox, RT Raines Functional evolution of ribonuclease inhibitor: Insights from birds and reptiles.  Journal of molecular biology, 426 (17) 2014: 3041-3056

Jason R Gallant, Lindsay L Traeger, Jeremy D Volkening, Howell Moffett, Po-Hao Chen, Carl D Novina, George N Phillips, Rene Anand, Gregg B Wells, Matthew Pinch, Robert Güth, Graciela A Unguez, James S Albert, Harold H Zakon, Manoj P Samanta, Michael R Sussman Genomic basis for the convergent evolution of electric organs.  Science 344 (6191), 1522-1525 2014

H Cao, JD Walton, P Brumm, GN Phillips Structure and substrate specificity of a eukaryotic fucosidase from Fusarium graminearum.  Journal of Biological Chemistry, 289 (37) 2014: 25624-25638

KK Desai, CA Bingman, CL Cheng, GN Phillips, RT Raines Structure of RNA 3′-phosphate cyclase bound to substrate RNA.  RNA, 20 (10) 2014: 1560-1566

Sherif I Elshahawi, Theresa A Ramelot, Jayaraman Seetharaman, Jing Chen, Shanteri Singh, Yunhuang Yang, Kari Pederson, Madan K Kharel, Rong Xiao, Scott Lew, Ragothaman M Yennamalli, Mitchell D Miller, Fengbin Wang, Liang Tong, Gaetano T Montelione, Michael A Kennedy, Craig A Bingman, Haining Zhu, George N Phillips Jr, Jon S Thorson Structure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19.  ACS chemical biology, 9 (10) 2014: 2347-2358

Jeremy R Lohman, Ming Ma, Marianne E Cuff, Lance Bigelow, Jessica Bearden, Gyorgy Babnigg, Andrzej Joachimiak, George N Phillips, Ben Shen The crystal structure of BlmI as a model for nonribosomal peptide synthetase peptidyl carrier proteins.  Proteins: Structure, Function, and Bioinformatics, 82(7) 2014: 1210-1218

Fengbin Wang, Shanteri Singh, Jianjun Zhang, Tyler D Huber, Kate E Helmich, Manjula Sunkara, Katherine A Hurley, Randal D Goff, Craig A Bingman, Andrew J Morris, Jon S Thorson, George N Phillips Understanding molecular recognition of promiscuity of thermophilic methionine adenosyltransferase sMAT from Sulfolobus solfataricus.  FEBS Journal, 281 (18) 2014: 4224-4239

R Yennamalli, R Arangarasan, A Bryden, M Gleicher, GN Phillips Jr Using a commodity high-definition television for collaborative structural biology.  Journal of applied crystallography , 47 (3) 2014: 1153-1157

Burgie, S.E., Walker, J.M., Phillips, G.N., Jr, Vierstra, R.D. A photo-labile thioether linkage to phycoviolobilin provides the foundation for the blue/green photocycles in DXCF-cyanobacteriochromes.  Structure, 21(1) 2013: 88-97

Daily MD, Yu H, Phillips GN Jr, Cui Q. Allosteric activation transitions in enzymes and biomolecular motors: insights from atomistic and coarse-grained simulations.  Top Curr Chem., 337 2013: 139-64

Wang F, Zhou M, Singh S, Yennamalli RM, Bingman CA, Thorson JS, Phillips GN Jr. Crystal structure of SsfS6, the putative C-glycosyltransferase involved in SF2575 biosynthesis.  Proteins, 81(7) 2013: 1277-82

Smith DW, Han MR, Park JS, Kim KR, Yeom T, Lee JY, Kim do J, Bingman CA, Kim HJ, Jo K, Han BW, Phillips GN Jr. Crystal structure of the protein from Arabidopsis thaliana gene At5g06450, a putative DnaQ-like exonuclease domain-containing protein with homohexameric assembly.  Proteins, 81(9) 2013: 1669-75

Singh S, Chang A, Helmich KE, Bingman CA, Wrobel RL, Beebe ET, Makino SI, Aceti DJ, Dyer K, Hura GL, Sunkara M, Morris AJ, Phillips GN Jr, Thorson JS. Structural and Functional Characterization of CalS11, a TDP-Rhamnose 3'-O-Methyltransferase Involved in Calicheamicin Biosynthesis.  ACS Chem Biol. 2013

Bianchetti CM, Brumm P, Smith RW, Dyer K, Hura GL, Rutkoski TJ, Phillips GN Jr. Structure and mechanism of Endoglucanase D from Clostridium cellulovorans.  J Mol Biol., 425(22) 2013: 4267-85

Lohman JR, Bingman CA, Phillips GN Jr, Shen B. Structure of the bifunctional acyltransferase/decarboxylase LnmK from the leinamycin biosynthetic pathway revealing novel activity for a double-hot-dog fold.  Biochemistry, 52(5) 2013: 902-11

Desai KK, Bingman CA, Phillips GN Jr, Raines RT. Structures of the noncanonical RNA ligase RtcB reveal the mechanism of histidine guanylylation.  Biochemistry, 52(15) 2013: 2518-25

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

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

Phillips Lab Website

  • B.A., Rice University Biochemistry and Chemistry (1974)
  • Ph.D., Rice University Biochemistry (1976)
  • Department of Chemistry
  • Keck Center for Quantitative Biomedical Sciences
  • Structure and dynamics of proteins, computational biology.
Email: georgep@rice.edu
Phone: (713) 348-6951
Office: George R. Brown Hall, W200Q