Photo of Gerhard Wagner,  PhD

Gerhard Wagner, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-3213
Fax: (617) 432-4383


wagner@hms.harvard.edu

Gerhard Wagner, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Elkan Blout Professor of Biological Chemistry and Molecular Pharmacology, Biological Chemistry and Molecular Pharmacology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

The research in the Wagner laboratory is focused on protein structure, dynamics and stability, and on the relation of these to protein function. The primary research tool is Nuclear Magnetic Resonance (NMR) spectroscopy. The research is focused on T-cell proteins (CD2, CD58, CD3, TCR, CD2BP2, Nck) and proteins involved in eukaryotic translation initiation (eIF4E, 4EBP, eIF4G, eIF4A, eIF1, eIF1A, eIF5, eIF5B). We also work on proteins important for transcriptional activation (transcriptional activator/coactivator interactions) and on apoptosis proteins from the Bcl-2 family and proteins located in the outer mitochondrial membrane. We are generally interested in identifying small-molecule inhibitors of protein-protein interactions and their potential use as anti-cancer agents. We also are developing a clinical metabolomics platform that jointly uses NMR and mass spectroscopy metabolite-based disease profiling and biomarker identification, targeting chronic myelogenous leukemia.

Publications

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  • O'Day E, Le MT, Imai S, Tan SM, Kirchner R, Arthanari H, Hofmann O, Wagner G, Lieberman J. An RNA-binding Protein, Lin28, Recognizes and Remodels G-quartets in the MicroRNAs (miRNAs) and mRNAs It Regulates. J Biol Chem 2015; 290:17909-22. PubMed
  • Sekiyama N, Arthanari H, Papadopoulos E, Rodriguez-Mias RA, Wagner G, Léger-Abraham M. Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1. Proc Natl Acad Sci U S A 2015. PubMed
  • Mallis RJ, Bai K, Arthanari H, Hussey RE, Handley M, Li Z, Chingozha L, Duke-Cohan JS, Lu H, Wang JH, Zhu C, Wagner G, Reinherz EL. Pre-TCR ligand binding impacts thymocyte development before 留硫TCR expression. Proc Natl Acad Sci U S A 2015; 112:8373-8. PubMed
  • Leigh KE, Sharma M, Mansueto MS, Boeszoermenyi A, Filman DJ, Hogle JM, Wagner G, Coen DM, Arthanari H. Structure of a herpesvirus nuclear egress complex subunit reveals an interaction groove that is essential for viral replication. Proc Natl Acad Sci U S A 2015. PubMed
  • Das DK, Feng Y, Mallis RJ, Li X, Keskin DB, Hussey RE, Brady SK, Wang JH, Wagner G, Reinherz EL, Lang MJ. Force-dependent transition in the T-cell receptor 硫-subunit allosterically regulates peptide discrimination and pMHC bond lifetime. Proc Natl Acad Sci U S A 2015; 112:1517-22. PubMed
  • Hiraishi H, Oatman J, Haller SL, Blunk L, McGivern B, Morris J, Papadopoulos E, Gutierrez W, Gordon M, Bokhari W, Ikeda Y, Miles D, Fellers J, Asano M, Wagner G, Tazi L, Rothenburg S, Brown SJ, Asano K. Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression. Nucleic Acids Res 2014; 42:10321-30. PubMed
  • Hagn F, Wagner G. Structure refinement and membrane positioning of selectively labeled OmpX in phospholipid nanodiscs. J Biomol NMR 2014. PubMed
  • Akabayov SR, Akabayov B, Wagner G. Human Translation Initiation Factor eIF4G1 Possesses a Low-Affinity ATP Binding Site Facing the ATP-Binding Cleft of eIF4A in the eIF4G/eIF4A Complex. Biochemistry 2014; 53:6422-5. PubMed
  • Takeuchi K, Sun ZY, Li S, Gal M, Wagner G. NMR resonance assignments of the catalytic domain of human serine/threonine phosphatase calcineurin in unligated and PVIVIT-peptide-bound states. Biomol NMR Assign 2014. PubMed
  • Yi T, Kabha E, Papadopoulos E, Wagner G. 4EGI-1 targets breast cancer stem cells by selective inhibition of translation that persists in CSC maintenance, proliferation and metastasis. 2014; 5:6028-37. PubMed
  • Linser R, Gelev V, Hagn F, Arthanari H, Hyberts SG, Wagner G. Selective methyl labeling of eukaryotic membrane proteins using cell-free expression. J Am Chem Soc 2014; 136:11308-10. PubMed
  • Papadopoulos E, Jenni S, Kabha E, Takrouri KJ, Yi T, Salvi N, Luna RE, Gavathiotis E, Mahalingam P, Arthanari H, Rodriguez-Mias R, Yefidoff-Freedman R, Aktas BH, Chorev M, Halperin JA, Wagner G. Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G. Proc Natl Acad Sci U S A 2014; 111:E3187-95. PubMed
  • Gal M, Li S, Luna RE, Takeuchi K, Wagner G. The LxVP and PxIxIT NFAT motifs bind jointly to overlapping epitopes on calcineurin's catalytic domain distant to the regulatory domain. Structure 2014; 22:1016-27. PubMed
  • Mahalingam P, Takrouri K, Chen T, Sahoo R, Papadopoulos E, Chen L, Wagner G, Aktas BH, Halperin JA, Chorev M. Synthesis of Rigidified eIF4E/eIF4G Inhibitor-1 (4EGI-1) Mimetic and Their in Vitro Characterization as Inhibitors of Protein-Protein Interaction. J Med Chem 2014. PubMed
  • Yi T, Zhai B, Yu Y, Kiyotsugu Y, Raschle T, Etzkorn M, Seo HC, Nagiec M, Luna RE, Reinherz EL, Blenis J, Gygi SP, Wagner G. Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci U S A 2014; 111:E2182-90. PubMed
  • Brazin KN, Mallis RJ, Li C, Keskin DB, Arthanari H, Gao Y, Wu SL, Karger BL, Wagner G, Reinherz EL. Constitutively oxidized CxxC motifs within the CD3 heterodimeric ectodomains of the T cell receptor complex enforce the conformation of juxtaposed segments. J Biol Chem 2014. PubMed
  • Avnir Y, Tallarico AS, Zhu Q, Bennett AS, Connelly G, Sheehan J, Sui J, Fahmy A, Huang CY, Cadwell G, Bankston LA, McGuire AT, Stamatatos L, Wagner G, Liddington RC, Marasco WA. Molecular signatures of hemagglutinin stem-directed heterosubtypic human neutralizing antibodies against influenza A viruses. PLoS Pathog. 2014; 10:e1004103. PubMed
  • Takrouri K, Chen T, Papadopoulos E, Sahoo R, Kabha E, Chen H, Cantel S, Wagner G, Halperin JA, Aktas BH, Chorev M. Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors. Eur J Med Chem 2014; 77:361-77. PubMed
  • Luna RE, Akabayov SR, Ziarek JJ, Wagner G. Examining weak protein-protein interactions in start codon recognition via NMR spectroscopy. FEBS J 2014; 281:1965-73. PubMed
  • Yefidoff-Freedman R, Chen T, Sahoo R, Chen L, Wagner G, Halperin JA, Aktas BH, Chorev M. 3-substituted indazoles as configurationally locked 4EGI-1 mimetics and inhibitors of the eIF4E/eIF4G interaction. Chembiochem 2014; 15:595-611. PubMed
  • Schmidt JC, Arthanari H, Boeszoermenyi A, Dashkevich NM, Wilson-Kubalek EM, Monnier N, Markus M, Oberer M, Milligan RA, Bathe M, Wagner G, Grishchuk EL, Cheeseman IM. The kinetochore-bound ska1 complex tracks depolymerizing microtubules and binds to curved protofilaments. Dev Cell 2012; 23:968-80. PubMed
  • Chen L, Aktas BH, Wang Y, He X, Sahoo R, Zhang N, Denoyelle S, Kabha E, Yang H, Freedman RY, Supko JG, Chorev M, Wagner G, Halperin JA. Tumor suppression by small molecule inhibitors of translation initiation. 2012; 3:869-81. PubMed
  • Luna RE, Arthanari H, Hiraishi H, Nanda J, Martin-Marcos P, Markus MA, Akabayov B, Milbradt AG, Luna LE, Seo HC, Hyberts SG, Fahmy A, Reibarkh M, Miles D, Hagner PR, O'Day EM, Yi T, Marintchev A, Hinnebusch AG, Lorsch JR, Asano K, Wagner G. The C-terminal domain of eukaryotic initiation factor 5 promotes start codon recognition by its dynamic interplay with eIF1 and eIF2硫. Cell Rep 2012; 1:689-702. PubMed
  • Milbradt AG, Kulkarni M, Yi T, Takeuchi K, Sun ZY, Luna RE, Selenko P, Näär AM, Wagner G. Structure of the VP16 transactivator target in the Mediator. Nat Struct Mol Biol 2011; 18:410-5. PubMed
  • Kang S, Kwon H, Wen H, Song Y, Frueh D, Ahn HC, Yoo SH, Wagner G, Park S. Global dynamic conformational changes in the suppressor domain of IP3 receptor by stepwise binding of the two lobes of calmodulin. FASEB J 2011; 25:840-50. PubMed
  • Shaw BF, Arthanari H, Narovlyansky M, Durazo A, Frueh DP, Pollastri MP, Lee A, Bilgicer B, Gygi SP, Wagner G, Whitesides GM. Neutralizing Positive Charges at the Surface of a Protein Lowers Its Rate of Amide Hydrogen Exchange without Altering Its Structure or Increasing Its Thermostability. J Am Chem Soc 2010. PubMed
  • Miao B, Skidan I, Yang J, Lugovskoy A, Reibarkh M, Long K, Brazell T, Durugkar KA, Maki J, Ramana CV, Schaffhausen B, Wagner G, Torchilin V, Yuan J, Degterev A. Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains. Proc Natl Acad Sci U S A 2010; 107:20126-31. PubMed
  • Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, Christofk HR, Wagner G, Rabinowitz JD, Asara JM, Cantley LC. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 2010; 329:1492-9. PubMed
  • Kim ST, Touma M, Takeuchi K, Sun ZY, Dave VP, Kappes DJ, Wagner G, Reinherz EL. Distinctive CD3 heterodimeric ectodomain topologies maximize antigen-triggered activation of alpha beta T cell receptors. J Immunol 2010; 185:2951-9. PubMed
  • Hiller S, Abramson J, Mannella C, Wagner G, Zeth K. The 3D structures of VDAC represent a native conformation. Trends Biochem Sci 2010; 35:514-21. PubMed
  • Takeuchi K, Heffron G, Sun ZY, Frueh DP, Wagner G. Nitrogen-detected CAN and CON experiments as alternative experiments for main chain NMR resonance assignments. J Biomol NMR 2010; 47:271-82. PubMed
  • Raschle T, Hiller S, Etzkorn M, Wagner G. Nonmicellar systems for solution NMR spectroscopy of membrane proteins. Curr Opin Struct Biol 2010; 20:471-9. PubMed
  • Takeuchi K, Sun ZY, Park S, Wagner G. Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity. Biochemistry 2010; 49:5634-41. PubMed
  • Takeuchi K, Frueh DP, Sun ZY, Hiller S, Wagner G. CACA-TOCSY with alternate 13C-12C labeling: a 13Calpha direct detection experiment for mainchain resonance assignment, dihedral angle information, and amino acid type identification. J Biomol NMR 2010; 47:55-63. PubMed
  • Hiller S, Malia TJ, Garces RG, Orekhov VY, Wagner G. Backbone and ILV side chain methyl group assignments of the integral human membrane protein VDAC-1. Biomol NMR Assign 2010; 4:29-32. PubMed
  • Takeuchi K, Frueh DP, Hyberts SG, Sun ZY, Wagner G. High-resolution 3D CANCA NMR experiments for complete mainchain assignments using C(alpha) direct detection. J Am Chem Soc 2010; 132:2945-51. PubMed
  • Hyberts SG, Takeuchi K, Wagner G. Poisson-gap sampling and forward maximum entropy reconstruction for enhancing the resolution and sensitivity of protein NMR data. J Am Chem Soc 2010; 132:2145-7. PubMed
  • Wagner G. A topical issue: production and labeling of biological macromolecules for NMR investigations. J Biomol NMR 2010; 46:1-2. PubMed
  • Zhou P, Wagner G. Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies. J Biomol NMR 2010; 46:23-31. PubMed
  • Raschle T, Hiller S, Yu TY, Rice AJ, Walz T, Wagner G. Structural and functional characterization of the integral membrane protein VDAC-1 in lipid bilayer nanodiscs. J Am Chem Soc 2009; 131:17777-9. PubMed
  • Kim ST, Takeuchi K, Sun ZY, Touma M, Castro CE, Fahmy A, Lang MJ, Wagner G, Reinherz EL. The alphabeta T cell receptor is an anisotropic mechanosensor. J Biol Chem 2009; 284:31028-37. PubMed
  • Hyberts SG, Frueh DP, Arthanari H, Wagner G. FM reconstruction of non-uniformly sampled protein NMR data at higher dimensions and optimization by distillation. J Biomol NMR 2009; 45:283-94. PubMed
  • Frueh DP, Leed A, Arthanari H, Koglin A, Walsh CT, Wagner G. Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 2009; 45:311-8. PubMed
  • Hiller S, Ibraghimov I, Wagner G, Orekhov VY. Coupled decomposition of four-dimensional NOESY spectra. J Am Chem Soc 2009; 131:12970-8. PubMed
  • Frueh DP, Arthanari H, Koglin A, Walsh CT, Wagner G. A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 2009; 131:12880-1. PubMed
  • Hiller S, Wagner G. The role of solution NMR in the structure determinations of VDAC-1 and other membrane proteins. Curr Opin Struct Biol 2009; 19:396-401. PubMed
  • Yu Y, Marintchev A, Kolupaeva VG, Unbehaun A, Veryasova T, Lai SC, Hong P, Wagner G, Hellen CU, Pestova TV. Position of eukaryotic translation initiation factor eIF1A on the 40S ribosomal subunit mapped by directed hydroxyl radical probing. Nucleic Acids Res 2009; 37:5167-82. PubMed
  • Song L,Sun ZY,Coleman KE,Zwick MB,Gach JS,Wang JH,Reinherz EL,Wagner G,Kim M. Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface. Proc Natl Acad Sci U S A 2009; 106:9057-62. PubMed
  • Yoffe Y,Leger M,Zinoviev A,Zuberek J,Darzynkiewicz E,Wagner G,Shapira M. Evolutionary changes in the Leishmania eIF4F complex involve variations in the eIF4E-eIF4G interactions. Nucleic Acids Res 2009; 37:3243-53. PubMed
  • Hemond M,Rothstein TL,Wagner G. Fas apoptosis inhibitory molecule contains a novel beta-sandwich in contact with a partially ordered domain. J Mol Biol 2009; 386:1024-37. PubMed
  • Thakur JK,Arthanari H,Yang F,Chau KH,Wagner G,Naar AM. Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p. J Biol Chem 2008; 284:4422-8. PubMed
  • Marintchev A,Edmonds KA,Marintcheva B,Hendrickson E,Oberer M,Suzuki C,Herdy B,Sonenberg N,Wagner G. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 2009; 136:447-60. PubMed
  • Bodner-Adler B,Bartl M,Wagner G. Intravenous leiomyomatosis of the uterus with pulmonary metastases or a case with benign metastasizing leiomyoma? Anticancer Res 2009; 29:495-6. PubMed
  • Takeuchi K,Sun ZY,Wagner G. Alternate 13C-12C labeling for complete mainchain resonance assignments using C alpha direct-detection with applicability toward fast relaxing protein systems. J Am Chem Soc 2008; 130:17210-1. PubMed
  • Billeter M,Wagner G,Wuthrich K. Solution NMR structure determination of proteins revisited. J Biomol NMR 2008; 42:155-8. PubMed
  • Kang S,Kang J,Kwon H,Frueh D,Yoo SH,Wagner G,Park S. Effects of redox potential and Ca2+ on the inositol 1,4,5-trisphosphate receptor L3-1 loop region: implications for receptor regulation. J Biol Chem 2008; 283:25567-75. PubMed
  • Hiller S,Garces RG,Malia TJ,Orekhov VY,Colombini M,Wagner G. Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science 2008; 321:1206-10. PubMed
  • Koglin A,Lohr F,Bernhard F,Rogov VV,Frueh DP,Strieter ER,Mofid MR,Guntert P,Wagner G,Walsh CT,Marahiel MA,Dotsch V. Structural basis for the selectivity of the external thioesterase of the surfactin synthetase. Nature 2008; 454:907-11. PubMed
  • Frueh DP,Arthanari H,Koglin A,Vosburg DA,Bennett AE,Walsh CT,Wagner G. Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase. Nature 2008; 454:903-6. PubMed
  • Takeuchi K,Yang H,Ng E,Park SY,Sun ZY,Reinherz EL,Wagner G. Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity. J Mol Biol 2008; 380:704-16. PubMed
  • Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 2008; 4:313-21. PubMed
  • Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Naar AM. A nuclear receptor-like pathway regulating multidrug resistance in fungi. Nature 2008; 452:604-9. PubMed
  • Suzuki C, Garces RG, Edmonds KA, Hiller S, Hyberts SG, Marintchev A, Wagner G. PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. Proc Natl Acad Sci U S A 2008; 105:3274-9. PubMed
  • Selenko P, Frueh DP, Elsaesser SJ, Haas W, Gygi SP, Wagner G. In situ observation of protein phosphorylation by high-resolution NMR spectroscopy. Nat Struct Mol Biol 2008; 15:321-9. PubMed
  • Marintcheva B, Marintchev A, Wagner G, Richardson CC. Acidic C-terminal tail of the ssDNA-binding protein of bacteriophage T7 and ssDNA compete for the same binding surface. Proc Natl Acad Sci U S A 2008; 105:1855-60. PubMed
  • Reibarkh M, Yamamoto Y, Singh CR, del Rio F, Fahmy A, Lee B, Luna RE, Ii M, Wagner G, Asano K. Eukaryotic initiation factor (eIF) 1 carries two distinct eIF5-binding faces important for multifactor assembly and AUG selection. J Biol Chem 2007; 283:1094-103. PubMed
  • Sun ZY, Oh KJ, Kim M, Yu J, Brusic V, Song L, Qiao Z, Wang JH, Wagner G, Reinherz EL. HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity 2008; 28:52-63. PubMed
  • Lindqvist L, Oberer M, Reibarkh M, Cencic R, Bordeleau ME, Vogt E, Marintchev A, Tanaka J, Fagotto F, Altmann M, Wagner G, Pelletier J. Selective pharmacological targeting of a DEAD box RNA helicase. PLoS ONE 2008; 3:e1583. PubMed
  • Tsodikov OV, Ivanov D, Orelli B, Staresincic L, Shoshani I, Oberman R, Scharer OD, Wagner G, Ellenberger T. Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA. EMBO J 2007; 26:4768-76. PubMed
  • Zhong W, Dixit SB, Mallis RJ, Arthanari H, Lugovskoy AA, Beveridge DL, Wagner G, Reinherz EL. CTL recognition of a protective immunodominant influenza A virus nucleoprotein epitope utilizes a highly restricted Vbeta but diverse Valpha repertoire: functional and structural implications. J Mol Biol 2007; 372:535-48. PubMed
  • Catic A, Sun ZY, Ratner DM, Misaghi S, Spooner E, Samuelson J, Wagner G, Ploegh HL. Sequence and structure evolved separately in a ribosomal ubiquitin variant. EMBO J 2007; 26:3474-83. PubMed
  • Unbehaun A, Marintchev A, Lomakin IB, Didenko T, Wagner G, Hellen CU, Pestova TV. Position of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probing. EMBO J 2007; 26:3109-23. PubMed
  • Lejard V, Brideau G, Blais F, Salingcarnboriboon R, Wagner G, Roehrl MH, Noda M, Duprez D, Houillier P, Rossert J. Scleraxis and NFATc regulate the expression of the pro-alpha1(I) collagen gene in tendon fibroblasts. J Biol Chem 2007; 282:17665-75. PubMed
  • Ito T, Wagner G. Resonance assignments of the alpha subunit of human eukaryotic initiation factor 2 (heIF2alpha). J Biomol NMR 2006; 38:173. PubMed
  • Lai KP, Law AY, Yeung HY, Lee LS, Wagner GF, Wong CK. Induction of stanniocalcin-1 expression in apoptotic human nasopharyngeal cancer cells by p53. Biochem Biophys Res Commun 2007; 356:968-75. PubMed
  • Takeuchi K, Roehrl MH, Sun ZY, Wagner G. Structure of the Calcineurin-NFAT Complex: Defining a T Cell Activation Switch Using Solution NMR and Crystal Coordinates. Structure 2007; 15:587-597. PubMed
  • Selenko P, Wagner G. Looking into live cells with in-cell NMR spectroscopy. J Struct Biol 2007; 158:244-53. PubMed
  • Ellard JP, McCudden CR, Tanega C, James KA, Ratkovic S, Staples JF, Wagner GF. The respiratory effects of stanniocalcin-1 (STC-1) on intact mitochondria and cells: STC-1 uncouples oxidative phosphorylation and its actions are modulated by nucleotide triphosphates. Mol Cell Endocrinol 2006; 264:90-101. PubMed
  • Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, Gross JD, Degterev A, Yuan J, Chorev M, Halperin JA, Wagner G. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 2007; 128:257-67. PubMed
  • Selenko P, Serber Z, Gadea B, Ruderman J, Wagner G. Quantitative NMR analysis of the protein G B1 domain in Xenopus laevis egg extracts and intact oocytes. Proc Natl Acad Sci U S A 2006; 103:11904-9. PubMed
  • Yamamoto Y, Singh CR, Marintchev A, Hall NS, Hannig EM, Wagner G, Asano K. The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G. Proc Natl Acad Sci U S A 2005; 102:16164-9. PubMed
  • He C, Hus JC, Sun LJ, Zhou P, Norman DP, D. A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada. Mol Cell 2005; 20:117-29. PubMed
  • Marintchev A, Wagner G. eIF4G and CBP80 share a common origin and similar domain organization: implications for the structure and function of eIF4G. Biochemistry 2005; 44:12265-72. PubMed
  • Oberer M, Marintchev A, Wagner G. Structural basis for the enhancement of eIF4A helicase activity by eIF4G. Genes Dev 2005; 19:2212-23. PubMed
  • Sun ZY, Frueh DP, Selenko P, Hoch JC, Wagner G. Fast Assignment of (15)N-HSQC Peaks using High-Resolution 3D HNcocaNH Experiments with Non-Uniform Sampling. J Biomol NMR 2005; 33:43-50. PubMed
  • Natarajan A, Guo Y, Arthanari H, Wagner G, Halperin JA, Chorev M. Synthetic studies toward aryl-(4-aryl-4H-[1,2,4]triazole-3-yl)-amine from 1,3-diarylthiourea as urea mimetics. J Org Chem 2005; 70:6362-8. PubMed
  • Elkin SK, Ivanov D, Ewalt M, Ferguson CG, Hyberts SG, Sun ZY, Prestwich GD, Yuan J, Wagner G, Oettinger MA, Gozani OP. A PHD finger motif in the C terminus of RAG2 modulates recombination activity. J Biol Chem 2005; 280:28701-10. PubMed
  • Park S, Isaacson R, Kim HT, Silver PA, Wagner G. Ufd1 exhibits the AAA-ATPase fold with two distinct ubiquitin interaction sites. Structure Fold Des 2005; 13:995-1005. PubMed
  • Roehrl MH, Heffron GJ, Wagner G. Correspondence between spin-dynamic phases and pulse program phases of NMR spectrometers. J Magn Reson 2005; 174:325-30. PubMed
  • Cherepanov P, Sun ZY, Rahman S, Maertens G, Wagner G, Engelman A. Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75. Nat Struct Mol Biol 2005; 12:526-32. PubMed
  • Frueh DP, Ito T, Li JS, Wagner G, Glaser SJ, Khaneja N. Sensitivity enhancement in NMR of macromolecules by application of optimal control theory. J Biomol NMR 2005; 32:23-30. PubMed
  • Sun ZY, Hyberts SG, Rovnyak D, Park S, Stern AS, Hoch JC, Wagner G. High-resolution aliphatic side-chain assignments in 3D HCcoNH experiments with joint H-C evolution and non-uniform sampling. J Biomol NMR 2005; 32:55-60. PubMed
  • Ivanov D, Stone JR, Maki JL, Collins T, Wagner G. Mammalian SCAN domain dimer is a domain-swapped homolog of the HIV capsid C-terminal domain. Mol Cell 2005; 17:137-43. PubMed
  • Roehrl MH, Wang JY, Wagner G. Discovery of small-molecule inhibitors of the NFAT--calcineurin interaction by competitive high-throughput fluorescence polarization screening. Biochemistry 2004; 43:16067-75. PubMed
  • Roehrl MH, Wang JY, Wagner G. A general framework for development and data analysis of competitive high-throughput screens for small-molecule inhibitors of protein-protein interactions by fluorescence polarization. Biochemistry 2004; 43:16056-66. PubMed
  • Sun ZY, Kim ST, Kim IC, Fahmy A, Reinherz EL, Wagner G. Solution structure of the CD3epsilondelta ectodomain and comparison with CD3epsilongamma as a basis for modeling T cell receptor topology and signaling. Proc Natl Acad Sci U S A 2004; 101:16867-72. PubMed
  • Walters KJ, Goh AM, Wang Q, Wagner G, Howley PM. Ubiquitin family proteins and their relationship to the proteasome: a structural perspective. Biochim Biophys Acta 2004; 1695:73-87. PubMed
  • Marintchev A, Wagner G. Translation initiation: structures, mechanisms and evolution. Q Rev Biophys 2005; 37:197-284. PubMed
  • Chatwood LL, M. NMR structure of the flavin domain from soluble methane monooxygenase reductase from Methylococcus capsulatus (Bath). Biochemistry 2004; 43:11983-91. PubMed
  • Walensky LD, Kung AL, Escher I, Malia TJ, Barbuto S, Wright RD, Wagner G, Verdine GL, Korsmeyer SJ. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 2004; 305:1466-70. PubMed
  • Rovnyak D, Frueh DP, Sastry M, Sun ZY, Stern AS, Hoch JC, Wagner G. Accelerated acquisition of high resolution triple-resonance spectra using non-uniform sampling and maximum entropy reconstruction. J Magn Reson 2004; 170:15-21. PubMed
  • Ito T, Marintchev A, Wagner G. Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B. Structure Fold Des 2004; 12:1693-704. PubMed
  • Rovnyak D, Hoch JC, Stern AS, Wagner G. Resolution and sensitivity of high field nuclear magnetic resonance spectroscopy. J Biomol NMR 2004; 30:1-10. PubMed
  • Kato M, Ito T, Wagner G, Ellenberger T. A molecular handoff between bacteriophage T7 DNA primase and T7 DNA polymerase initiates DNA synthesis. J Biol Chem 2004; 279:30554-62. PubMed
  • von der Haar T, Gross JD, Wagner G, McCarthy JE. The mRNA cap-binding protein eIF4E in post-transcriptional gene expression. Nat Struct Mol Biol 2004; 11:503-11. PubMed
  • Roehrl MH, Kang S, Aramburu J, Wagner G, Rao A, Hogan PG. Selective inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with small organic molecules. Proc Natl Acad Sci U S A 2004; 101:7554-9. PubMed
  • Natarajan A, Moerke N, Fan YH, Chen H, Christ WJ, Wagner G, Halperin JA. Synthesis of fluorescein labeled 7-methylguanosinemonophosphate. Bioorg Med Chem Lett 2004; 14:2657-60. PubMed
  • Gross JD, Moerke NJ, von der Haar T, Lugovskoy AA, Sachs AB, McCarthy JE, Wagner G. Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Cell 2003; 115:739-50. PubMed
  • Lomakin IB, Kolupaeva VG, Marintchev A, Wagner G, Pestova TV. Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probing. Genes Dev 2003; 17:2786-97. PubMed
  • Freund C, K. Structural investigations of a GYF domain covalently linked to a proline-rich peptide. J Biomol NMR 2003; 27:143-9. PubMed
  • Kim PW, Sun ZY, Blacklow SC, Wagner G, Eck MJ. A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8. Science 2003; 301:1725-8. PubMed
  • Gozani O, Karuman P, Jones DR, Ivanov D, Cha J, Lugovskoy AA, Baird CL, Zhu H, Field SJ, Lessnick SL, Villasenor J, Mehrotra B, Chen J, Rao VR, Brugge JS, Ferguson CG, Payrastre B, Myszka DG, Cantley LC, Wagner G, Divecha N, Prestwich GD, Yuan J. The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor. Cell 2003; 114:99-111. PubMed
  • Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ. Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2. Nat Struct Biol 2003; 10:504-12. PubMed
  • Marintchev A, Kolupaeva VG, Pestova TV, Wagner G. Mapping the binding interface between human eukaryotic initiation factors 1A and 5B: a new interaction between old partners. Proc Natl Acad Sci U S A 2003; 100:1535-40. PubMed
  • Freund C, K. Dynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules. EMBO J 2002; 21:5985-95. PubMed
  • Freedman SJ, Sun ZY, Poy F, Kung AL, Livingston DM, Wagner G, Eck MJ. Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha. Proc Natl Acad Sci U S A 2002; 99:5367-72. PubMed
  • Lugovskoy AA, Degterev AI, Fahmy AF, Zhou P, Gross JD, Yuan J, Wagner G. A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors. J Am Chem Soc 2002; 124:1234-40. PubMed
  • Kim M, Sun ZY, Byron O, Campbell G, Wagner G, Wang J, Reinherz EL. Molecular dissection of the CD2-CD58 counter-receptor interface identifies CD2 Tyr86 and CD58 Lys34 residues as the functional "hot spot". J Mol Biol 2001; 312:711-20. PubMed
  • Sun ZJ, Kim KS, Wagner G, Reinherz EL. Mechanisms contributing to T cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3 epsilon gamma heterodimer. Cell 2001; 105:913-23. PubMed
  • Degterev A, Lugovskoy A, Cardone M, Mulley B, Wagner G, Mitchison T, Yuan J. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat Cell Biol 2001; 3:173-82. PubMed
  • Kim KS, Sun ZY, Wagner G, Reinherz EL. Heterodimeric CD3epsilongamma extracellular domain fragments: production, purification and structural analysis. J Mol Biol 2000; 302:899-916. PubMed
  • Reinherz EL, Tan K, Tang L, Kern P, Liu J, Xiong Y, Hussey RE, Smolyar A, Hare B, Zhang R, Joachimiak A, Chang HC, Wagner G, Wang J. The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 1999; 286:1913-21. PubMed
  • del R. Solution structure of the hRPABC14.4 subunit of human RNA polymerases. Nat Struct Biol 1999; 6:1039-42. PubMed
  • Hershey PE, McWhirter SM, Gross JD, Wagner G, Alber T, Sachs AB. The Cap-binding protein eIF4E promotes folding of a functional domain of yeast translation initiation factor eIF4G1. J Biol Chem 1999; 274:21297-304. PubMed
  • Walters KJ, Gassner GT, Lippard SJ, Wagner G. Structure of the soluble methane monooxygenase regulatory protein B. Proc Natl Acad Sci U S A 1999; 96:7877-82. PubMed
  • Freund C, D. The GYF domain is a novel structural fold that is involved in lymphoid signaling through proline-rich sequences. Nat Struct Biol 1999; 6:656-60. PubMed
  • Lin Y, Fletcher CM, Zhou J, Allis CD, Wagner G. Solution structure of the catalytic domain of GCN5 histone acetyltransferase bound to coenzyme A. Nature 1999; 400:86-9. PubMed
  • Wang JH, Smolyar A, Tan K, Liu JH, Kim M, Sun ZY, Wagner G, Reinherz EL. Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors. Cell 1999; 97:791-803. PubMed
  • Sun ZY, D. Functional glycan-free adhesion domain of human cell surface receptor CD58: design, production and NMR studies. EMBO J 1999; 18:2941-9. PubMed
  • Hare BJ, Wyss DF, Osburne MS, Kern PS, Reinherz EL, Wagner G. Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor. Nat Struct Biol 1999; 6:574-81. PubMed
  • Jasanoff A, Song S, Dinner AR, Wagner G, Wiley DC. One of two unstructured domains of Ii becomes ordered in complexes with MHC class II molecules. Immunity 1999; 10:761-8. PubMed
  • Fletcher CM, Pestova TV, Hellen CU, Wagner G. Structure and interactions of the translation initiation factor eIF1. EMBO J 1999; 18:2631-7. PubMed
  • Chou JJ, Li H, Salvesen GS, Yuan J, Wagner G. Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell 1999; 96:615-24. PubMed
  • Jasanoff A, Wagner G, Wiley DC. Structure of a trimeric domain of the MHC class II-associated chaperonin and targeting protein Ii. EMBO J 1998; 17:6812-8. PubMed
  • Kupce E, Schmidt P, Rance M, Wagner G. Adiabatic mixing in the liquid state. J Magn Reson 1999; 135:361-7. PubMed
  • D. New approaches to structure determination by NMR spectroscopy. Curr Opin Struct Biol 1998; 8:619-23. PubMed
  • Chou JJ, Matsuo H, Duan H, Wagner G. Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment. Cell 1998; 94:171-80. PubMed
  • McGuire AM, Matsuo H, Wagner G. Internal and overall motions of the translation factor eIF4E: cap binding and insertion in a CHAPS detergent micelle. J Biomol NMR 1998; 12:73-88. PubMed
  • Fletcher CM, Wagner G. The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein. Protein Sci 1998; 7:1639-42. PubMed
  • Zhu J, Shibasaki F, Price R, Guillemot JC, Yano T, D. Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1. Cell 1998; 93:851-61. PubMed
  • Fletcher CM, McGuire AM, Gingras AC, Li H, Matsuo H, Sonenberg N, Wagner G. 4E binding proteins inhibit the translation factor eIF4E without folded structure. Biochemistry 1998; 37:9-15. PubMed
  • Ferentz AE, Opperman T, Walker GC, Wagner G. Dimerization of the UmuD' protein in solution and its implications for regulation of SOS mutagenesis. Nat Struct Biol 1997; 4:979-83. PubMed
  • Walters KJ, Dayie KT, Reece RJ, Ptashne M, Wagner G. Structure and mobility of the PUT3 dimer. Nat Struct Biol 1997; 4:744-50. PubMed
  • Markus MA, Matsudaira P, Wagner G. Refined structure of villin 14T and a detailed comparison with other actin-severing domains. Protein Sci 1997; 6:1197-209. PubMed
  • Wyss DF, Choi JS, Li J, Knoppers MH, Willis KJ, Arulanandam AR, Smolyar A, Reinherz EL, Wagner G. Conformation and function of the N-linked glycan in the adhesion domain of human CD2. Science 1995; 269:1273-8. PubMed
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