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New NMR methods development. molecular recognition. growth factors. protein: nucleic acid complexes. molecular dynamics. structural bioinformatics. protein foldingThe general aim of our research is to use NMR spectroscopy as a tool for protein engineering and structural bioinformatics. We develop new methods for protein solution structure determination and apply these techniques to proteins of pharmaceutical or medical interest. The combined methods of site-directed mutagenesis. NMR spectroscopy. and conformational energy calculations are being used to (1) determine three dimensional structures of small proteins in solution. (2) determine the structures of protein-protein. protein-receptor. and protein-nucleic acid complexes. (3) characterize effects of amino acid substitutions on protein structure. stability. and dynamics. (4) direct efforts to design and engineer proteins and provide information for rational drug design. and (5) study the molecular mechanisms by which proteins fold into their biologically-active conformations. We are currently working on structure determination and refinement of several DNA-and RNA-binding proteins. We have recently determined solution structures of an IgG-binding domain of staphylococcal Protein A and of an RNA-binding protein from E.coli which is overproduced in response to cold shock (Cold Shock Protein A). We have characterized structural changes in these molecules which are required for binding to IgG proteins or to nucleic acids. Nuclear relaxation time measurements are used to characterize intramolecular motion in these small proteins. This research has important implications in the fields of protein physical chemistry. molecular design. receptor-ligand interactions. and oncogenesis. We are attempting to develop a general strategy for using structural analysis by NMR as a means of deciphering the biochemical functions of new genes identified in the human genome project. Selected PublicationsEletsky A, Sukumaran DK, Xiao R, Acton TB, Rost B, Montelione GT, Szyperski T. (2009) NMR structure of protein YvyC from Bacillus subtilis reveals unexpected structural similarity between two PFAM families. Proteins. Apr 20. [Epub ahead of print] Sharma S, Zheng H, Huang YJ, Ertekin A, Hamuro Y, Rossi P, Tejero R, Acton TB, Xiao R, Jiang M, Zhao L, Ma LC, Swapna GV, Aramini JM, Montelione GT.Construct optimization for protein NMR structure analysis using amide hydrogen/deuterium exchange mass spectrometry. Proteins. (2009) Feb 2. [Epub ahead of print] Montelione GT, Arrowsmith C, Girvin ME, Kennedy MA, Markley JL, Powers R, Prestegard JH, Szyperski T. (2009) Unique opportunities for NMR methods in structural genomics. J Struct Funct Genomics. 10(2):101-6. Schwede T, Sali A, Honig B, Levitt M, Berman HM, Jones D, Brenner SE, Burley SK, Das R, Dokholyan NV, Dunbrack RL Jr, Fidelis K, Fiser A, Godzik A, Huang YJ, Humblet C, Jacobson MP, Joachimiak A, Krystek SR Jr, Kortemme T, Kryshtafovych A, Montelione GT, Moult J, Murray D, Sanchez R, Sosnick TR, Standley DM, Stouch T, Vajda S, Vasquez M, Westbrook JD, Wilson IA. (2009) Outcome of a workshop on applications of protein models in biomedical research. Nair R, Liu J, Soong TT, Acton TB, Everett JK, Kouranov A, Fiser A, Godzik A, Jaroszewski L, Orengo C, Montelione GT, Rost B. (2009) Structural genomics is the largest contributor of novel structural leverage. J Struct Funct Genomics. 10(2):181-91. Bertonati C, Punta M, Fischer M, Yachdav G, Forouhar F, Zhou W, Kuzin AP, Seetharaman J, Abashidze M, Ramelot TA, Kennedy MA, Cort JR, Belachew A, Hunt JF, Tong L, Montelione GT, Rost B. (2009) Structural genomics reveals EVE as a new ASCH/PUA-related domain. Proteins. 75(3):760-73. Liu G, Forouhar F, Eletsky A, Atreya HS, Aramini JM, Xiao R, Huang YJ, Abashidze M, Seetharaman J, Liu J, Rost B, Acton T, Montelione GT, Hunt JF, Szyperski T. (2009) NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan UFM1-UBA5-UFC1 ubiquination pathway. Price WN 2nd, Chen Y, Handelman SK, Neely H, Manor P, Karlin R, Nair R, Liu J, Baran M, Everett J, Tong SN, Forouhar F, Swaminathan SS, Acton T, Xiao R, Luft JR, Lauricella A, DeTitta GT, Rost B, Montelione GT, Hunt JF. (2009) Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol. 27(1):51-7. Parish D, Benach J, Liu G, Singarapu KK, Xiao R, Acton T, Su M, Bansal S, Prestegard JH, Hunt J, Montelione GT, Szyperski T. (2008) Protein chaperones Q8ZP25_SALTY from Salmonella typhimurium and HYAE_ECOLI from Escherichia coli exhibit thioredoxin-like structures despite lack of canonical thioredoxin active site sequence motif. J Struct Funct Genomics. 9(1-4):41-9. Vorobiev SM, Su M, Seetharaman J, Huang YJ, Chen CX, Maglaqui M, Janjua H, Proudfoot M, Yakunin A, Xiao R, Acton TB, Montelione GT, Tong L. (2008) Crystal structure of human retinoblastoma binding protein 9. Proteins. 74(2):526-9. Rossi P, Aramini JM, Xiao R, Chen CX, Nwosu C, Owens LA, Maglaqui M, Nair R, Fischer M, Acton TB, Honig B, Rost B, Montelione GT. (2008) Structural elucidation of the Cys-His-Glu-Asn proteolytic relay in the secreted CHAP domain enzyme from the human pathogen Staphylococcus saprophyticus. Proteins. 74(2):515-9. Ramelot TA, Raman S, Kuzin AP, Xiao R, Ma LC, Acton TB, Hunt JF, Montelione GT, Baker D, Kennedy MA. (2008) Improving NMR protein structure quality by Rosetta refinement: A molecular replacement study. Proteins. 75(1):147-67. Vila JA, Aramini JM, Rossi P, Kuzin A, Su M, Seetharaman J, Xiao R, Tong L, Montelione GT, Scheraga HA. (2008) Quantum chemical 13C(alpha) chemical shift calculations for protein NMR structure determination, refinement, and validation. Proc Natl Acad Sci U S A. 105(38):14389-94. Das K, Ma LC, Xiao R, Radvansky B, Aramini J, Zhao L, Marklund J, Kuo RL, Twu KY, Arnold E, Krug RM, Montelione GT.(2008) Structural basis for suppression of a host antiviral response by influenza A virus. Proc Natl Acad Sci U S A. 105(35):13093-8. Aramini JM, Rossi P, Huang YJ, Zhao L, Jiang M, Maglaqui M, Xiao R, Locke J, Nair R, Rost B, Acton TB, Inouye M, Montelione GT. (2008) Solution NMR structure of the NlpC/P60 domain of lipoprotein Spr from Escherichia coli: structural evidence for a novel cysteine peptidase catalytic triad. Biochemistry. 47(37):9715-7. Cort JR, Ramelot TA, Murray D, Acton TB, Ma LC, Xiao R, Montelione GT, Kennedy MA. (2008) Structure of an acetyl-CoA binding protein from Staphylococcus aureus representing a novel subfamily of GCN5-related N-acetyltransferase-like proteins. J Struct Funct Genomics. 9(1-4):7-20. Huang YJ, Hang D, Lu LJ, Tong L, Gerstein MB, Montelione GT. v Targeting the human cancer pathway protein interaction network by structural genomics. Mol Cell Proteomics. (10):2048-60. Aramini JM, Sharma S, Huang YJ, Swapna GV, Ho CK, Shetty K, Cunningham K, Ma LC, Zhao L, Owens LA, Jiang M, Xiao R, Liu J, Baran MC, Acton TB, Rost B, Montelione GT. (2008) Solution NMR structure of the SOS response protein YnzC from Bacillus subtilis. Proteins. 72(1):526-30. Forouhar F, Abashidze M, Xu H, Grochowski LL, Seetharaman J, Hussain M, Kuzin A, Chen Y, Zhou W, Xiao R, Acton TB, Montelione GT, Galinier A, White RH, Tong L. (2008) Molecular insights into the biosynthesis of the F420 coenzyme. J Biol Chem. 283(17):11832-40. Singarapu KK, Xiao R, Acton T, Rost B, Montelione GT, Szyperski T. (2008) NMR structure of the peptidyl-tRNA hydrolase domain from Pseudomonas syringae expands the structural coverage of the hydrolysis domains of class 1 peptide chain release factors. Proteins. 71(2):1027-31. Structural Genomics Consortium; China Structural Genomics Consortium; Northeast Structural Genomics Consortium. (2008) Protein production and purification. Nat Methods. 5(2):135-46. Review. Erratum in: Nat Methods. 2008 Apr;5(4):369. Hallberg, B Martin [added]. Burley SK, Joachimiak A, Montelione GT, Wilson IA. (2008) Contributions to the NIH-NIGMS protein structure initiative from the PSI production centers. Structure. 16(1):5-11. Singarapu KK, Xiao R, Sukumaran DK, Acton T, Montelione GT, Szyperski T. (2008) NMR structure of protein Cgl2762 from Corynebacterium glutamicum implicated in DNA transposition reveals a helix-turn-helix motif attached to a flexibly disordered leucine zipper. Proteins. 70(4):1650-4. Benach J, Wang L, Chen Y, Ho CK, Lee S, Seetharaman J, Xiao R, Acton TB, Montelione GT, Deng H, Sun R, Tong L. (2007) Structural and functional studies of the abundant tegument protein ORF52 from murine gammaherpesvirus 68. J Biol Chem. 282(43):31534-41. Liu J, Montelione GT, Rost B. (2007) Novel leverage of structural genomics. Nat Biotechnol. 25(8):849-51. Bhattacharya A, Wunderlich Z, Monleon D, Tejero R, Montelione GT. (2008) Assessing model accuracy using the homology modeling automatically software. Proteins. 70(1):105-18. Andrec M, Snyder DA, Zhou Z, Young J, Montelione GT, Levy RM. (2007) A large data set comparison of protein structures determined by crystallography and NMR: statistical test for structural differences and the effect of crystal packing. Proteins. 69(3):449-65. Forouhar F, Kuzin A, Seetharaman J, Lee I, Zhou W, Abashidze M, Chen Y, Yong W, Janjua H, Fang Y, Wang D, Cunningham K, Xiao R, Acton TB, Pichersky E, Klessig DF, Porter CW, Montelione GT, Tong L. (2007) Functional insights from structural genomics. J Struct Funct Genomics. 8(2-3):37-44. Lu LJ, Sboner A, Huang YJ, Lu HX, Gianoulis TA, Yip KY, Kim PM, Montelione GT, Gerstein MB. Aramini JM, Huang YJ, Swapna GV, Cort JR, Rajan PK, Xiao R, Shastry R, Acton TB, Liu J, Rost B, Kennedy MA, Montelione GT. (2007) Solution NMR structure of Escherichia coli ytfP expands the structural coverage of the UPF0131 protein domain family. Proteins. 68(3):789-95. Aramini JM, Rossi P, Anklin C, Xiao R, Montelione GT. (2007) Microgram-scale protein structure determination by NMR. Nat Methods. 4(6):491-3. Yin C, Khan JA, Swapna GV, Ertekin A, Krug RM, Tong L, Montelione GT. (2007) Conserved surface features form the double-stranded RNA-binding site of non-structural protein 1 (NS1) from influenza A and B viruses. J Biol Chem. 282(28):20584-92. Vorobiev SM, Neely H, Seetharaman J, Ma LC, Xiao R, Acton TB, Montelione GT, Tong L. (2007) Crystal structure of AGR_C_4470p from Agrobacterium tumefaciens. Protein Sci. 16(3):535-8. Singarapu KK, Liu G, Xiao R, Bertonati C, Honig B, Montelione GT, Szyperski T. (2007) NMR structure of protein yjbR from Escherichia coli reveals 'double-wing' DNA binding motif. Bhattacharya A, Tejero R, Montelione GT. (2007) Evaluating protein structures determined by structural genomics consortia. Proteins. 66(4):778-95. Mercier KA, Baran M, Ramanathan V, Revesz P, Xiao R, Montelione GT, Powers R. (2006) FAST-NMR: functional annotation screening technology using NMR spectroscopy. J Am Chem Soc. 128(47):15292-9. Greenfield NJ, Huang YJ, Swapna GV, Bhattacharya A, Rapp B, Singh A, Montelione GT, Hitchcock-DeGregori SE. (2006) Solution NMR structure of the junction between tropomyosin molecules: implications for actin binding and regulation. J Mol Biol. 364(1):80-96. Berman HM, Burley SK, Chiu W, Sali A, Adzhubei A, Bourne PE, Bryant SH, Dunbrack RL Jr, Fidelis K, Frank J, Godzik A, Henrick K, Joachimiak A, Heymann B, Jones D, Markley JL, Moult J, Montelione GT, Orengo C, Rossmann MG, Rost B, Saibil H, Schwede T, Standley DM, Westbrook JD. (2006) Outcome of a workshop on archiving structural models of biological macromolecules. Structure. 14(8):1211-7. Kornhaber GJ. Snyder D. Moseley HN. Montelione GT. (2006) Identification of zinc-ligated cysteine residues based on 13Calpha and 13Cbeta chemical shift data. J Biomol NMR. 34(4):259-69. Baran MC. Moseley HN. Aramini JM. Bayro MJ. Monleon D. Locke JY. Montelione GT. (2006) SPINS: a laboratory information management system for organizing and archiving intermediate and final results from NMR protein structure determinations. Proteins. 62(4):843-51. Huang YJ. Tejero R. Powers R. Montelione GT. (2006) A topology-constrained distance network algorithm for protein structure determination from NOESY data. Proteins. 62(3):587-603. Rossi P. Theresa Ramelot SS. Xiao R. Ho CK. Ma LC. Acton TB. Kennedy MA. Montelione GT. (2005) 1H. 13C. and 15N resonance assignments for the protein coded by gene locus BB0938 of Bordetella ronchiseptica. J Biomol NMR. 33(3):197. Aramini JM. Swapna GV. Huang YJ. Rajan PK. Xiao R. Shastry R. Acton TB. Cort JR. Kennedy MA. Montelione GT. (2005) 1H. 13C. and 15N resonance assignments for Escherichia coli ytfP. a member of the broadly conserved UPF0131 protein domain family. J Biomol NMR. 33(3):197. No abstract available. Forouhar F. Hussain M. Farid R. Benach J. Abashidze M. Edstrom WC. Vorobiev SM. Xiao R. Acton TB. Fu Z. Kim JJ. Miziorko HM. Montelione GT. Hunt JF. (2006) Crystal structures of two bacterial 3-hydroxy-3-methylglutaryl-CoA lyases suggest a common catalytic mechanism among a family of TIM barrel metalloenzymes cleaving carbon-carbon bonds. J Biol Chem. 281(11):7533-45. Snyder DA. Chen Y. Denissova NG. Acton T. Aramini JM. Ciano M. Karlin R. Liu J. Manor P. Rajan PA. Rossi P. Swapna GV. Xiao R. Rost B. Hunt J. Montelione GT. (2005) Comparisons of NMR spectral quality and success in crystallization demonstrate that NMR and X-ray crystallography are complementary methods for small protein structure determination. J Am Chem Soc. 127(47):16505-11. Liu G. Shen Y. Xiao R. Acton T. Ma LC. Joachimiak A. Montelione GT. Szyperski T. (2006) NMR structure of protein yqbG from Bacillus subtilis reveals a novel alpha-helical protein fold. Proteins. 62(1):288-91. Huang YJ. Montelione GT. (2005) Structural biology: proteins flex to function. Nature. N438(7064):36-7. Powers R. Mirkovic N. Goldsmith-Fischman S. Acton TB. Chiang Y. Huang YJ. Ma L. Rajan PK. Cort JR. Kennedy MA. Liu J. Rost B. Honig B. Murray D. Montelione GT. (2005) Solution structure of Archaeglobus fulgidis peptidyl-tRNA hydrolase (Pth2) provides evidence for an extensive conserved family of Pth2 enzymes in archea. bacteria. and eukaryotes. Protein Sci. 14(11):2849-61. Forouhar F. Lee IS. Vujcic J. Vujcic S. Shen J. Vorobiev SM. Xiao R. Acton TB. Montelione GT. Porter CW. Tong L. (2005) Structural and functional evidence for Bacillus subtilis PaiA as a novel N1-spermidine/spermine acetyltransferase. J Biol Chem. 280(48):40328-36. Douglas SM. Montelione GT. Gerstein M. (2005) PubNet: a flexible system for visualizing literature derived networks. Genome Biol. 6(9):R80. Bachhawat P. Swapna GV. Montelione GT. Stock AM. (2005) Mechanism of activation for transcription factor PhoB suggested by different modes of dimerization in the inactive and active states. Structure. 13(9):1353-63. Liu G. Aramini J. Atreya HS. Eletsky A. Xiao R. Acton T. Ma L. Montelione GT. Szyperski T. (2005) GFT NMR based resonance assignment for the 21 kDa human protein UFC1. J Biomol NMR. 32(3):261. N Liu G. Shen Y. Atreya HS. Parish D. Shao Y. Sukumaran DK. Xiao R. Yee A. Lemak A. Bhattacharya A. Acton TA. Arrowsmith CH. Montelione GT. Szyperski T. (2005) NMR data collection and analysis protocol for high-throughput protein structure determination. Proc Natl Acad Sci U S A. 102(30):10487-92. Liu G. Li Z. Chiang Y. Acton T. Montelione GT. Murray D. Szyperski T. (2005) High-quality homology models derived from NMR and X-ray structures of E. coli proteins YgdK and Suf E suggest that all members of the YgdK/Suf E protein family are enhancers of cysteine desulfurases. Protein Sci. 14(6):1597-608. Benach J. Edstrom WC. Lee I. Das K. Cooper B. Xiao R. Liu J. Rost B. Acton TB. Montelione GT. Hunt JF. (2005) The 2.35 A structure of the TenA homolog from Pyrococcus furiosus supports an enzymatic function in thiamine metabolism. Acta Crystallogr D Biol Crystallogr. 61(Pt 5):589-98. Snyder DA. Bhattacharya A. Huang YJ. Montelione GT. (2005) Assessing precision and accuracy of protein structures derived from NMR data. Proteins. 59(4):655-61. Review. Snyder DA. Montelione GT. (2005) Clustering algorithms for identifying core atom sets and for assessing the precision of protein structure ensembles. Proteins. 59(4):673-86. Acton TB. Gunsalus KC. Xiao R. Ma LC. Aramini J. Baran MC. Chiang YW. Climent T. Cooper B. Denissova NG. Douglas SM. Everett JK. Ho CK. Macapagal D. Rajan PK. Shastry R. Shih LY. Swapna GV. Wilson M. Wu M. Gerstein M. Inouye M. Hunt JF. Montelione GT. (2005) Robotic cloning and protein production platform of the Northeast Structural Genomics Consortium. Methods Enzymol. 394:210-43. |
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