研究领域
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.
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Select item 25356641
Crystal structure of human protein N-terminal glutamine amidohydrolase, an initial component of the N-end rule pathway.
Park MS, Bitto E, Kim KR, Bingman CA, Miller MD, Kim HJ, Han BW, Phillips GN Jr.
PLoS One. 2014 Oct 30;9(10):e111142. doi: 10.1371/journal.pone.0111142. eCollection 2014.
PMID: 25356641 [PubMed - in process] Free PMC Article
Select item 25354690
Structure of a cupin protein Plu4264 from Photorhabdus luminescens subsp. laumondii TTO1 at 1.35 Å resolution.
Weerth RS, Michalska K, Bingman CA, Yennamalli RM, Li H, Jedrzejczak R, Wang F, Babnigg G, Joachimiak A, Thomas MG, Phillips GN Jr.
Proteins. 2015 Feb;83(2):383-8. doi: 10.1002/prot.24705. Epub 2014 Dec 18.
PMID: 25354690 [PubMed - in process]
Select item 25164811
Biochemical characterization and crystal structures of a fungal family 3 β-glucosidase, Cel3A from Hypocrea jecorina.
Karkehabadi S, Helmich KE, Kaper T, Hansson H, Mikkelsen NE, Gudmundsson M, Piens K, Fujdala M, Banerjee G, Scott-Craig JS, Walton JD, Phillips GN Jr, Sandgren M.
J Biol Chem. 2014 Nov 7;289(45):31624-37. doi: 10.1074/jbc.M114.587766. Epub 2014 Aug 27.
PMID: 25164811 [PubMed - indexed for MEDLINE]
Select item 25161697
Evolution of substrate specificity in bacterial AA10 lytic polysaccharide monooxygenases.
Book AJ, Yennamalli RM, Takasuka TE, Currie CR, Phillips GN Jr, Fox BG.
Biotechnol Biofuels. 2014 Aug 6;7:109. doi: 10.1186/1754-6834-7-109. eCollection 2014.
PMID: 25161697 [PubMed] Free PMC Article
Select item 25161314
Structure of RNA 3'-phosphate cyclase bound to substrate RNA.
Desai KK, Bingman CA, Cheng CL, Phillips GN Jr, Raines RT.
RNA. 2014 Oct;20(10):1560-6. doi: 10.1261/rna.045823.114. Epub 2014 Aug 26.
PMID: 25161314 [PubMed - indexed for MEDLINE]
Select item 25086049
Structure and substrate specificity of a eukaryotic fucosidase from Fusarium graminearum.
Cao H, Walton JD, Brumm P, Phillips GN Jr.
J Biol Chem. 2014 Sep 12;289(37):25624-38. doi: 10.1074/jbc.M114.583286. Epub 2014 Aug 1.
PMID: 25086049 [PubMed - indexed for MEDLINE]
Select item 25079510
Structure-guided functional characterization of enediyne self-sacrifice resistance proteins, CalU16 and CalU19.
Elshahawi SI, Ramelot TA, Seetharaman J, Chen J, Singh S, Yang Y, Pederson K, Kharel MK, Xiao R, Lew S, Yennamalli RM, Miller MD, Wang F, Tong L, Montelione GT, Kennedy MA, Bingman CA, Zhu H, Phillips GN Jr, Thorson JS.
ACS Chem Biol. 2014 Oct 17;9(10):2347-58. doi: 10.1021/cb500327m. Epub 2014 Aug 13.
PMID: 25079510 [PubMed - in process]
Select item 25050442
The crystal structure of BlmI as a model for nonribosomal peptide synthetase peptidyl carrier proteins.
Lohman JR, Ma M, Cuff ME, Bigelow L, Bearden J, Babnigg G, Joachimiak A, Phillips GN Jr, Shen B.
Proteins. 2014 Jul;82(7):1210-8.
PMID: 25050442 [PubMed - in process] Free PMC Article
Select item 24970089
Nonhuman genetics. Genomic basis for the convergent evolution of electric organs.
Gallant JR, Traeger LL, Volkening JD, Moffett H, Chen PH, Novina CD, Phillips GN Jr, Anand R, Wells GB, Pinch M, Güth R, Unguez GA, Albert JS, Zakon HH, Samanta MP, Sussman MR.
Science. 2014 Jun 27;344(6191):1522-5. doi: 10.1126/science.1254432.
PMID: 24970089 [PubMed - indexed for MEDLINE]
Select item 24941155
Functional evolution of ribonuclease inhibitor: insights from birds and reptiles.
Lomax JE, Bianchetti CM, Chang A, Phillips GN Jr, Fox BG, Raines RT.
J Mol Biol. 2014 Aug 26;426(17):3041-56. doi: 10.1016/j.jmb.2014.06.007. Epub 2014 Jun 15.
PMID: 24941155 [PubMed - indexed for MEDLINE] Free PMC Article
Select item 24931334
Effectiveness and limitations of local structural entropy optimization in the thermal stabilization of mesophilic and thermophilic adenylate kinases.
Moon S, Bannen RM, Rutkoski TJ, Phillips GN Jr, Bae E.
Proteins. 2014 Oct;82(10):2631-42. doi: 10.1002/prot.24627. Epub 2014 Jun 28.
PMID: 24931334 [PubMed - in process]
Select item 24904249
Using a commodity high-definition television for collaborative structural biology.
Yennamalli R, Arangarasan R, Bryden A, Gleicher M, Phillips GN Jr.
J Appl Crystallogr. 2014 May 29;47(Pt 3):1153-1157. eCollection 2014 Jun 1.
PMID: 24904249 [PubMed] Free PMC Article
Select item 24649856
Understanding molecular recognition of promiscuity of thermophilic methionine adenosyltransferase sMAT from Sulfolobus solfataricus.
Wang F, Singh S, Zhang J, Huber TD, Helmich KE, Sunkara M, Hurley KA, Goff RD, Bingman CA, Morris AJ, Thorson JS, Phillips GN Jr.
FEBS J. 2014 Sep;281(18):4224-39. doi: 10.1111/febs.12784. Epub 2014 Apr 7.
PMID: 24649856 [PubMed - indexed for MEDLINE]
Select item 24615904
An integrated approach for thermal stabilization of a mesophilic adenylate kinase.
Moon S, Jung DK, Phillips GN Jr, Bae E.
Proteins. 2014 Sep;82(9):1947-59. doi: 10.1002/prot.24549. Epub 2014 Mar 24.
PMID: 24615904 [PubMed - in process]
Select item 24435797
A tRNA splicing operon: Archease endows RtcB with dual GTP/ATP cofactor specificity and accelerates RNA ligation.
Desai KK, Cheng CL, Bingman CA, Phillips GN Jr, Raines RT.
Nucleic Acids Res. 2014 Apr;42(6):3931-42. doi: 10.1093/nar/gkt1375. Epub 2014 Jan 16.
PMID: 24435797 [PubMed - indexed for MEDLINE] Free PMC Article
Select item 23751954
Structure, dynamics, and specificity of endoglucanase D from Clostridium cellulovorans.
Bianchetti CM, Brumm P, Smith RW, Dyer K, Hura GL, Rutkoski TJ, Phillips GN Jr.
J Mol Biol. 2013 Nov 15;425(22):4267-85. doi: 10.1016/j.jmb.2013.05.030. Epub 2013 Jun 8.
PMID: 23751954 [PubMed - indexed for MEDLINE] Free PMC Article
Select item 23662776
Structural and functional characterization of CalS11, a TDP-rhamnose 3'-O-methyltransferase involved in calicheamicin biosynthesis.
Singh S, Chang A, Helmich KE, Bingman CA, Wrobel RL, Beebe ET, Makino S, Aceti DJ, Dyer K, Hura GL, Sunkara M, Morris AJ, Phillips GN Jr, Thorson JS.
ACS Chem Biol. 2013 Jul 19;8(7):1632-9. doi: 10.1021/cb400068k. Epub 2013 May 23.
PMID: 23662776 [PubMed - indexed for MEDLINE] Free PMC Article
Select item 23616405
Crystal structure of the protein from Arabidopsis thaliana gene At5g06450, a putative DnaQ-like exonuclease domain-containing protein with homohexameric assembly.
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.
Proteins. 2013 Sep;81(9):1669-75. doi: 10.1002/prot.24315. Epub 2013 Jun 17.
PMID: 23616405 [PubMed - indexed for MEDLINE]
Select item 23560983
Structures of the noncanonical RNA ligase RtcB reveal the mechanism of histidine guanylylation.
Desai KK, Bingman CA, Phillips GN Jr, Raines RT.
Biochemistry. 2013 Apr 16;52(15):2518-25. doi: 10.1021/bi4002375. Epub 2013 Apr 5.
PMID: 23560983 [PubMed - indexed for MEDLINE] Free PMC Article
Select item 23526584
Crystal structure of SsfS6, the putative C-glycosyltransferase involved in SF2575 biosynthesis.
Wang F, Zhou M, Singh S, Yennamalli RM, Bingman CA, Thorson JS, Phillips GN Jr.
Proteins. 2013 Jul;81(7):1277-82. doi: 10.1002/prot.24289. Epub 2013 Apr 20.
PMID: 23526584 [PubMed - indexed for MEDLINE] Free PMC Article
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