Skip to main content
SpringerLink
Log in

Two-, Three-, and Four-Dimensional Nuclear Magnetic Resonance Spectroscopy of Protein Pharmaceuticals

  • Chapter
Physical Methods to Characterize Pharmaceutical Proteins

Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 7))

  • 242 Accesses

Abstract

In the past decade, nuclear magnetic resonance (NMR) spectroscopy and related computational techniques have evolved to such a degree that it is now possible to completely assign the [1H]-NMR spectrum and, using this information, determine the three-dimensional structure of a protein of more than 100 residues (Clore and Gronenborn, 1991a; Inagaki, 1990; Wagner et al., 1992; Wüthrich, 1986, 1989a,b, 1990). Consequently, it has become as important a tool in the structural determination of proteins as X-ray crystallography. The interest in NMR has been further accelerated by the advent of biotechnology, where it is now possible to produce proteins for use as therapeutic agents.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abdel-Meguid, S. S., Shieh, H.-S., Smith, W. W., Dayringer, H. E., Violand, B. N., and Bentle, L. A., 1987, Three-dimensional structure of a genetically engineered variant of porcine growth hormone, Proc. Natl. Acad. Sci. USA 84:6434–6437.

    PubMed  CAS  Google Scholar 

  • Archer, S. J., Ikura, M., Torchia, D., and Bax, A., 1992, An alternative 3D NMR technique for correlating backbone 15N with side chain Hβ resonances in larger proteins, J. Magn. Resort. 95:636–641.

    Google Scholar 

  • Aue, W. P., Bartholdi, E., and Ernst, R. R., 1976, Two-dimensional spectroscopy. Application to nuclear magnetic resonance, J. Chem. Phys. 64:2229–2246.

    CAS  Google Scholar 

  • Baker, E. N., Blundell, T. L., Cutfield, J. E, Cutfield, S. M., Dodson, E. J., Dodson, G. G., Crowfoot Hodgkin, D. M., Hubbard, R. E., Isaacs, N. W., Reynolds, C. D., Sakabe, K., Sakabe, N., and Vijayan, N. M., 1988, The structure of Zn pig insulin crystals at 1.5 Å resolution, Philos. Trans. R. Soc. London B 319:369–456.

    CAS  Google Scholar 

  • Baldwin, E. T., Weber, I. T., St. Charles, R., Xuan, J. C., Appella, E., Yamada, M., Matsushima, K., Edwards, B. F., Clore, G. M., and Gronenborn, A. M., 1991, Crystal structure of interleukin 8: Symbiosis of NMR and crystallography, Proc. Natl. Acad. Sci. USA 88:502–506.

    PubMed  CAS  Google Scholar 

  • Bax, A., and Davis, D. G., 1985a, Practical aspects of two-dimensional transverse NOE spectroscopy, J. Magn. Reson. 63:207–213.

    CAS  Google Scholar 

  • Bax, A., and Davis, D. G., 1985b, MLEV-17 based two-dimensional homonuclear magnetization transfer spectroscopy, J. Magn. Reson. 65:355–360.

    CAS  Google Scholar 

  • Bax, A., and Morris, G., 1981, An improved method for heteronuclear chemical shift correlation by two-dimensional NMR, J. Magn. Reson. 42:501–505.

    CAS  Google Scholar 

  • Bax, A., and Subramanian, S., 1986, Sensitivity-enhanced two-dimensional heteronuclear shift correlation NMR spectroscopy, J. Magn. Reson. 67:565–569.

    CAS  Google Scholar 

  • Bax, A., and Summers, M., 1986, lH and 13C assignments from sensitivity-enhanced detection of heteronuclear multiple-bond connectivity by 2D multuple quantum NMR, J. Am. Chem. Soc. 108:2093–2094.

    CAS  Google Scholar 

  • Bax, A., DeJong, P. G., Mehlkopf, A. F., and Smidt, J., 1980, Separation of the different orders of NMR multiple-quantum transitions by the use of pulsed field gradients, Chem. Phys. Lett. 69:567–570.

    CAS  Google Scholar 

  • Bax, A., Clore, G. M., and Gronenborn, A. M., 1990, 1H-1Hcorrelation via isotropic mixing of 13C magnetization, a new three-dimensional approach for assigning 1H and 13C spectra of 13C-enriched proteins, J. Magn. Reson. 88:425–431.

    CAS  Google Scholar 

  • Bernstein, R., Cieslar, C., Ross, A., Oschkinat, H., Freund, J., and Holak, T., 1993, Computer-assisted assignment of multidimensional NMR spectra of proteins: Application to 3D NOESY-HMQC and TOCSY-HMQC spectra, J. Biomol. NMR 3:245–251.

    CAS  Google Scholar 

  • Bodenhausen, G., Kogler, H., and Ernst, R. R., 1984, Selection of coherence-transfer pathways in NMR pulse experiments, J. Magn. Reson. 58:370–388.

    CAS  Google Scholar 

  • Boelens, R., Vuister, G. W., Koning, T. M. G., and Kaptein, R., 1989, Observation of spin diffusion in biomolecules by three-dimensional NOE-NOE spectroscopy, J. Am. Chem. Soc. 111:8525–8526.

    CAS  Google Scholar 

  • Bothner-By, A. A., 1984, Structure determination of a tetrasaccharide: Transient nuclear overhauser effects in the rotating frame, J. Am. Chem. Soc. 106:811–813.

    CAS  Google Scholar 

  • Boucher, W., Laue, E. D., Campbell-Burk, S. L., and Domaille, P. J., 1992, Improved 4D NMR experiments for the assignment of backbone nuclei in 13C/15N labelled proteins, J. Biomol. NMR 2:631–637.

    CAS  Google Scholar 

  • Bradbury, J. H., and Ramesh, V., 1981, 1H NMR study of the histidine residues of insulin, J. Mol. Biol. 150:609–613.

    PubMed  CAS  Google Scholar 

  • Bradbury, J. H., and Ramesh, V., 1985, lH NMR studies of insulin. Assignment of resonances and properties of tyrosine residues, Biochem. J. 229:731–737.

    PubMed  CAS  Google Scholar 

  • Braun, W., 1987, Distance geometry and related methods for protein structure determination from NMR data, Quart. Rev. Biophys. 19:115–157.

    CAS  Google Scholar 

  • Braun, W., and Go, N., 1985, Calculation of protein conformation by proton-proton distance constraints: A new efficient algorithm. J. Mol. Biol. 186:611–626.

    PubMed  CAS  Google Scholar 

  • Breg, J., Boelens, R., Vuister, G. W., and Kaptein, R., 1990, 3D NOE-NOE spectroscopy of proteins. Observation of sequential 3D NOE cross peaks in arc repressor, J. Magn. Reson. 87:646–651.

    CAS  Google Scholar 

  • Briinger, A., and Karplus, M., 1991, Molecular dynamics simulations with experimental results, Acc. Chem. Res. 24:54–61.

    Google Scholar 

  • Campbell, I. D., Baron, M., Cooke, R. M., Dudgeon, T. J., Fallon, A., Harvey, T. S., and Tappin, M. J., 1990, Structure-function relationships in epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), Biochem. Pharmacol. 40: 35–40.

    PubMed  CAS  Google Scholar 

  • Carver, J. A., Cooke, R. M., Esposito, G., Campbell, I. D., Gregory, H., and Sheard, B., 1986, A high-resolution lH NMR study of the solution structure of human epidermal growth factor, FEBS Lett. 205:77–81.

    PubMed  CAS  Google Scholar 

  • Chary, K. V. R., Otting, G., and Wüthrich, K., 1991, Measurement of small heteronuclear 1H-15N coupling constants in 15N-labeled proteins by 3D HNNHAB-COSY., J. Magn. Reson. 93:218–224.

    CAS  Google Scholar 

  • Chothia, C., Levitt, M., and Richardson, D., 1981, Helix to helix packing in proteins, J. Mol. Biol. 145:215–250.

    PubMed  CAS  Google Scholar 

  • Chou, K.-C., Maggiora, G. M., Nemethy, G., and Scheraga, H. A., 1988, Energetics of the structure of the four alpha-helix bundle in proteins, Proc. Natl. Acad. Sci. USA 85: 4295–4299.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., and Gronenborn, A. M., 1982, Theory and applications of the transferred nuclear overhauser effect to the study of the conformations of small ligands bound to proteins, J. Magn. Reson. 48:402–417.

    CAS  Google Scholar 

  • Clore, G. M., and Gronenborn, A. M., 1983, Theory of the time-dependent transferred nuclear overhauser effect: Applications to structural analysis of ligand-protein complexes in solution, J. Magn. Resort. 53:423–442.

    CAS  Google Scholar 

  • Clore, G. M., and Gronenborn, A. M., 1991a, Structure of larger proteins in solution: Three-and four-dimensional heteronuclear NMR spectroscopy, Science 252:1390–1399.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., and Gronenborn, A. M., 1991b, Comparison of the solution nuclear magnetic resonance and crystal structures of interleukin-8. Possible implications for the mechanism of receptor binding, J. Mol. Biol. 217:611–620.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., and Gronenborn, A. M., 1991c, Comparison of the solution nuclear magnetic resonance and X-ray crystal structures of human recombinant interleukin-1β, J. Mol. Biol. 221:47–53.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Appella, E., Yamada, M., Matsushima, K., and Gronenborn, A. M., 1989, Determination of the secondary structure of interleukin-8 by nuclear magnetic resonance spectroscopy, J. Biol. Chem. 264:18907–18911.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Appella, E., Yamada, M., Matsushima, K., and Gronenborn, A. M., 1990a, Three-dimensional structure of interleukin 8 in solution, Biochemistry 29:1689–1696.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Driscoll, P. C., Wingfield, P. T., and Gronenborn, A. M., 1990b, Low resolution structure of interleukin-lβ in solution derived from 1H-15N heteronuclear three-dimensional nuclear magnetic resonance spectroscopy, J. Mol. Biol. 214: 811–817.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Driscoll, P. C., Wingfield, P. T., and Gronenborn, A. M., 1990c, Analysis of the backbone dynamics of interleukin-lβ using two-dimensional inverse detected heteronuclear 15N-lH NMR spectroscopy, Biochemistry 29:7387–7401.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Bax, A., Driscoll, P. C., Wingfield, P. T., and Gronenborn, A. M., 1990d, Assignment of the side-chain 1H and 13C resonances of interleukin-1β using double-and triple-resonance heteronuclear three-dimensional NMR spectroscopy, Biochemistry 29:8172–8184.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Bax, A., Wingfield, P. T., and Gronenborn, A. M., 1990e, Identification and localization of bound internal water in the solution structure of interleukin 1β by heteronuclear three-dimensional 1H rotating frame Overhauser 15N-1H miultiple quantum coherence NMR spectroscopy, Biochemistry 29:5671–5676.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Kay, L. E., Bax, A., and Gronenborn, A. M., 1991a, Four-dimensional 13C/13C-edited nuclear overhauser enhancement spectroscopy of a protein in solution: Application to interleukin 1β, Biochemistry 30:12–18.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Wingfield, P. T., and Gronenborn, A. M., 1991b, High-resolution three-dimensional structure of interleukin 1β in solution by three-and four-dimensional nuclear magnetic resonance spectroscopy, Biochemistry 30:2315–2323.

    PubMed  CAS  Google Scholar 

  • Clore, G. M., Bax, A., and Gronenborn, A. M., 1991c, Stereospecific assignment of β-methylene protons in larger proteins using 3D 15N-separated Hartmann-Hahn and 13C-separated rotating frame overhauser spectroscopy, J. Biomol NMR 1:13–22.

    PubMed  CAS  Google Scholar 

  • Cooke, R. M., Wilkinson, A. J., Baron, M., Pastore, A., Tappin, M. J., Campbell, I. D., Gregory, H., and Sheard, B., 1987, The solution structure of human epidermal growth factor, Nature 327:339–341.

    PubMed  CAS  Google Scholar 

  • Cooke, R. M., Tappin, M. J., Campbell, I. D., Kohda, D., Miyake, T., Fuwa, T., Miyazawa, Y., and Inagaki, F., 1990, Nuclear magnetic resonance studies of human epidermal growth factor, Eur. J. Biochem. 197:807–815.

    Google Scholar 

  • Crippen, G. M., 1981, Distance Geometry and Conformational Calculations, Chemometrics Research Studies Press, Letchworth, UK.

    Google Scholar 

  • Crippen, G. M., and Havel, T. F., 1988, Distance Geometry and Molecular Conformation, Wiley, New York.

    Google Scholar 

  • Croasmun, W. R., and Carlson, R. M. K. (eds.), 1987, Two-Dimensional NMR Spectroscopy. Applications for Chemists and Biochemists, Verlag Chemie, Berlin.

    Google Scholar 

  • De Marco, A., Menegatti, E., and Guarneri, M., 1983, Epidermal growth factor: Exposure and dynamics of the aromatic side chains as investigated by photo-CIDNP and variable temperature 1H NMR, FEBS Lett. 159:201–206.

    Google Scholar 

  • De Marco, A., Mayo, K. H., Bartolotti, F., Scalia, S., Menegatti, E., and Kaptein, R., 1986, Proton NMR and photochemically induced dynamic nuclear polarization studies of peptide fragments obtained by controlled proteolysis of mouse epidermal growth factor, J. Biol. Chem. 261:13510–13516.

    PubMed  Google Scholar 

  • Driscoll, P. C., Clore, G. M., Marion, D., Wingfield, P. T., and Gronenborn, A. M., 1990a, Complete resonance assignment for the polypeptide backbone of interleukin-1β using three-dimensional heteronuclear NMR spectroscopy, Biochemistry 29:3542–3556.

    PubMed  CAS  Google Scholar 

  • Driscoll, P. C., Gronenborn, A. M., Wingfield, P. T., and Clore, G. M., 1990b, Determination of the secondary structure and molecular topology of interleukin-lβ by use of two-and three-dimensional heteronuclear 15N-1H NMR spectroscopy, Biochemistry 29:4668–4682.

    PubMed  CAS  Google Scholar 

  • Dudgeon, T. J., Cooke, R. M., Baron, M., Campbell, I. D., Edwards, R. M., and Fallon, A., 1990, Structure-function analysis of epidermal growth factor: Site-directed mutagenesis and nuclear magnetic resonance, FEBS Lett. 261:392–396.

    PubMed  CAS  Google Scholar 

  • Ealick, S. E., Cook, W. J., Vijay-Kumar, S., Carson, M., Nagabhushan, T. L., Trotta, P. P., and Bugg, C. E., 1991, Three-dimensional structure of recombinant human interferon-γ, Science 252:698–702.

    PubMed  CAS  Google Scholar 

  • Emerson, S. D., and Montelione, G. T., 1992, 2D and 3D HCCH TOCSY experiments for determining 3J (Hα-Hβ) coupling constants of amino acid residues, J. Magn. Reson. 99:413–420.

    CAS  Google Scholar 

  • Englander, W., and Wand, S. J., 1987, Main-chain-directed strategy for the assignment of lH NMR spectra of proteins, Biochemistry 26:5953–5958.

    PubMed  CAS  Google Scholar 

  • Engler, D. A., Montelione, G. T., and Niyogi, S. K., 1990, Human epidermal growth factor. Distinct roles of tyrosine 37 and arginine 41 in receptor binding as determined by sitedirected mutagenesis and nuclear magnetic resoance spectroscopy, FEBS Lett. 271:47–50.

    PubMed  CAS  Google Scholar 

  • Ernst, R. R., Bodenhausen, G., and Wokaun, A., 1987, Principles of Nuclear Magnetic Resonance in One and Two Dimensions, Oxford University Press, New York.

    Google Scholar 

  • Fesik, S. W., 1988, Isotope-edited NMR spectroscopy, Nature 332:865–866.

    Google Scholar 

  • Fesik, S. W., 1993, NMR structure-based drug design, J. Biomol. NMR 3:261–269.

    PubMed  CAS  Google Scholar 

  • Fesik, S. W., and Zuiderweg, E. R. P., 1989, An approach for studying the active site of enzyme/inhibitor complexes using deuterated ligands and 2D NOE difference spectroscopy, J. Am. Chem. Soc. 111:5013–5015.

    CAS  Google Scholar 

  • Fesik, S. W., Luly, J. R., Erickson, J. W., and Abad-Zapatero, C., 1988, Isotope-edited proton NMR study on the structure of a pepsin/inhibitor complex, Biochemistry 27:8297–8301.

    PubMed  CAS  Google Scholar 

  • Fesik, S. W., Eaton, H. L., Olejniczak, E. T., Zuiderweg, E. R. P., McIntosh, L. P., and Dahlquist, F. W., 1990, 2D and 3D NMR spectroscopy employing 13C-13C magnetization transfer by isotropic mixing. Spin system identification in large proteins, J. Am. Chem. Soc. 112:886–888.

    CAS  Google Scholar 

  • Garrett, D. S., Powers, R., March, C. J., Frieden, E. A., Clore, G. M., and Gronenborn, A. M., 1992, Determination of the secondary structure and folding topology of human interleukin-4 using three-dimensional heteronuclear magnetic resonance spectroscopy, Biochemistry 31:4347–4353.

    PubMed  CAS  Google Scholar 

  • Gilson, M. K., and Honig, B., 1989, Destabilization of an alpha helix bundle protein by helix dipoles, Proc. Natl. Acad. Sci. USA 86:1524–1528.

    PubMed  CAS  Google Scholar 

  • Gronenborn, A. M., and Clore, G. M., 1989, Analysis of the relative contributions of the nuclear overhauser interproton distance restraints and the empirical energy function in the calculation of oligonucleotide structures using restrained molecular dynamics, Biochemistry 28:5978–5984.

    PubMed  CAS  Google Scholar 

  • Gronenborn, A. M., Clore, G. M., Schmeissner, U., and Wingfield, P., 1986, A 1H-NMR study of human interleukin-1β. Sequence-specific assignment of aromatic residues using site-directed mutant proteins, Eur. J. Biochem. 161:37–43.

    PubMed  CAS  Google Scholar 

  • Gronenborn, A. M., Wingfield, P. T., McDonald, H. R., Schmeissner, U., and Clore, G. M., 1988, Site directed mutants of human interleukin-lα: A lH NMR and receptor binding study, FEBS Lett. 231:135–138.

    PubMed  CAS  Google Scholar 

  • Grzesiek, S., and Bax, A., 1992, Improved 3D triple-resonance NMR techniques applied to a 31 kDa protein, J. Magn. Reson. 96:432–440.

    CAS  Google Scholar 

  • Grzesiek, S., Döbeli, H., Gentz, R., Garotta, G., Labhardt, A. M., and Bax, A., 1992a, 1H, 13C., and 15N NMR backbone assignments and secondary structure of human inter-feron-γ, Biochemistry 31:8180–8190.

    PubMed  CAS  Google Scholar 

  • Grzesiek, S., Ikura, M., Clore, G. M., Gronenborn, A. M., and Bax, A., 1992b, A 3D triple-resonance NMR technique for qualitative measurement of carbonyl-Hβ J couplings in isotopically enriched proteins, J. Magn. Reson. 96:215–221.

    CAS  Google Scholar 

  • Habazettl, J., Cieslar, C., Oschkinat, H., and Holak, T. A., 1990, 1H NMR assignments of side chain conformations in proteins using a high-dimensional potential in the simulated annealing calculations, FEBS Lett. 268:141–145.

    PubMed  CAS  Google Scholar 

  • Han, K. H., Ferretti, J. A., Niu, C. H., Lokeshwar, V., Clarke, R., and Katz, D., 1988, Conformational and receptor binding properties of human EGF and TGF-alpha second loop fragments, J. Mol. Recog. 1:116–123.

    CAS  Google Scholar 

  • Han, K. H., Syi, J. L., Brooks, B. R., and Ferretti, J. A., 1990, Solution conformations of the B-loop fragments of human transforming growth factor alpha and epidermal growth factor by 1H nuclear magnetic resonance and restrained molecular dynamics, Proc. Natl. Acad. Sci. USA 87:2818–2822.

    PubMed  CAS  Google Scholar 

  • Havel, T. F., 1991, An evaluation of computational strategies for use in the determination of protein structure from distance constraints obtained by nuclear magnetic resonance, Prog. Biophys. Mol. Biol. 56:43–78.

    PubMed  CAS  Google Scholar 

  • Havel, T., and Wüthrich, K., 1984, A distance geometry program for determining the structures of small proteins and other macromolecules from nuclear magnetic resonance measurements of intramolecular 1H-1H proximities in solution, Bull. Math. Biol. 46:673–698.

    CAS  Google Scholar 

  • Havel, T. F., and Wüthrich, K., 1985, An evaluation of the combined use of NMR and distance geometry for the determination of protein conformations in solution, J. Mol. Biol. 182:281–294.

    PubMed  CAS  Google Scholar 

  • Hommel, U., Dudgeon, T. J., Fallon, A., Edwards, R. M., and Campbell, I. D., 1991, Structure-function relationships in human epidermal growth factor studied by site-directed mutagenesis and 1H NMR, Biochemistry 30:8891–8898.

    PubMed  CAS  Google Scholar 

  • Hommel, U, Harvey, T. S., Driscoll, P. C., and Campbell, I. D., 1992, Human epidermal growth factor. High resolution solution structure and comparison with human transforming growth factor alpha, J. Mol. Biol. 227:271–282.

    PubMed  CAS  Google Scholar 

  • Hua, Q.-X., Chen, Y.-J., Wang, C.-C., Wang, D.-C., and Roberts, G. C. K., 1989, High resolution 1H NMR studies of des-(B26-B30)-insulin: Assignment of resonances and properties of aromatic residues, Biochim. Biophys. Acta 994:114–120.

    PubMed  CAS  Google Scholar 

  • Hurd, R. E., 1990, Gradient-enhanced spectroscopy, J. Magn. Reson. 87:422–428.

    CAS  Google Scholar 

  • Hurd, R. E., and John, B. K., 1991a, Gradient-enhanced proton-detected heteronuclear multiple-quantum coherence spectroscopy, J. Magn. Reson. 91:648–653.

    CAS  Google Scholar 

  • Hurd, R. E., and John, B. K., 1991b, Three-dimensional gradient-enhanced relay-edited proton spectroscopy, GREP-HMQC-COSY., J. Magn. Reson. 92:658–688.

    CAS  Google Scholar 

  • Ikebuchi, K., Wong, C. C., Clark, S. C., Ihle, J. N., Hirai, Y., and Ogawa, M., 1987, Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors, Proc. Natl. Acad. Sci. USA 84:9035–9039.

    PubMed  CAS  Google Scholar 

  • Ikura, M., Kay, L. E., and Bax, A., 1990, A novel approach for sequential assignment of 1H, 13C., and 15N spectra of larger proteins: Heteronuclear triple-resonance three-dimensional NMR spectroscopy. Application to calmodulin, Biochemistry 29:4659–4667.

    PubMed  CAS  Google Scholar 

  • Ikura, M., Kay, L. E., and Bax, A., 1991, Improved three-dimensional 1H-13C1H correlation spectroscopy of a 13C-labeled protein using constant-time evolution, J. Biomol. NMR 1:299–304.

    PubMed  CAS  Google Scholar 

  • Inagaki, F., 1990, Three-dimensional structures of proteins determined by two-dimensional NMR and distance geometry calculations, Cell Struct. Funct. 15:237–243.

    PubMed  CAS  Google Scholar 

  • Jeener, J., 1971, Ampere International Summer School, Basko Polje, Yugoslavia.

    Google Scholar 

  • Jorgensen, A. M. M., Kristensen, S. M., Led, J. J., and Balschmidt, P., 1992, Three-dimensional solution structure of an insulin dimer. A study of the B9(Asp) mutant of human insulin using nuclear magnetic resonance, distance geometry and restrained molecular dynamics, J. Mol. Biol. 227:1146–1163.

    PubMed  CAS  Google Scholar 

  • Kaptein, R., Boelens, R., Scheek, R. M., and van Gunsteren, W. F., 1988, Protein structures from NMR, Biochemistry 27:5389–5395.

    PubMed  CAS  Google Scholar 

  • Kato, K., Matsunaga, C., Odaka, A., Yamato, S., Tahaka, W., Shimada, I., and Arata, Y., 1991, Carbon-13 NMR study of switch-variant anti-dansyl antibodies: Antigen binding and domain-domain interactions, Biochemistry 30:6604–6610.

    PubMed  CAS  Google Scholar 

  • Kay, L. E., Clore, G. M., Bax, A., and Gronenborn, A. M., 1990a, Four-dimensional heteronuclear triple-resonance NMR spectroscopy of interleukin-1β in solution, Science 249:411–414.

    PubMed  CAS  Google Scholar 

  • Kay, L. E., Ikura, M., Tschudin, R., and Bax, A., 1990b, Three-dimensional triple-resonance NMR spectroscopy of isotopically enriched proteins, J. Magn. Reson. 89:496–514.

    CAS  Google Scholar 

  • Kay, L. E., Ikura, M., Zhu, G., and Bax, A., 1991, Four-dimensional heteronuclear triple-resonance NMR of isotopically enriched proteins for sequential assignment of backbone atoms, J. Magn. Reson. 91:422–428.

    CAS  Google Scholar 

  • Kay, L. E., Wittekind, M., McCoy, M. A., Friedrichs, M. S., and Mueller, L., 1992, 4D NMR triple resonance experiments for assignments of protein backbone nuclei using shared constant-time evolution periods, J. Magn. Reson. 98:443–450.

    CAS  Google Scholar 

  • Kessler, H., and Steuernagel, S., 1991, in: Peptide Pharmaceuticals, Approaches to the Design of Novel Drugs. Conformational Determination by NMR Spectroscopy (D. J. Ward, ed.), Elsevier, New York, pp. 18–46.

    Google Scholar 

  • Kessler, H., Gehrke, M., and Griesinger, C., 1988, Two-dimensional NMR spectroscopy: Background and overview of the experiments, Angew. Chem. Int. Ed. Engl. 27: 490–536.

    Google Scholar 

  • Kishimoto, T., and Hirano, T., 1988, Molecular regulation of B lymphocyte response, Annu. Rev. Immunol. 6:485–512.

    PubMed  CAS  Google Scholar 

  • Kline, A. D., and Justice, R. M., Jr., 1990, Complete sequence-specific lH NMR assignments for human insulin, Biochemistry 29:2906–2913.

    PubMed  CAS  Google Scholar 

  • Knegtel, R. M. A., Boelens, R., Ganadu, M. L., and Kaptein, R., 1991, The solution structure of a monoemeric insulin. A two-dimensional 1H NMR study of des-(B26-B30)-insulin in combination with distance geometry and restrained molecular dynamics, Eur. J. Biochem. 202:447–458.

    PubMed  CAS  Google Scholar 

  • Kohda, D., and Inagaki, F., 1988, Complete sequence-specific 1H nuclear magnetic resonance assignments for mouse epidermal growth factor, J. Biochem. (Tokyo) 103: 554–571.

    CAS  Google Scholar 

  • Kohda, D., and Inagaki, F., 1992a, Structure of epidermal growth factor bound to perdeuterated dodecylphosphocholine micelles determined by two-dimensional NMR and simulated annealing calculations, Biochemistry 31:677–685.

    PubMed  CAS  Google Scholar 

  • Kohda, D., and Inagaki, F., 1992b, Three-dimensional nuclear magnetic resonance structures of mouse epidermal growth factor in acidic and physiological pH solutions, Biochemistry 31:11928–11939.

    PubMed  CAS  Google Scholar 

  • Kohda, D., Go, N., Hayashi, K., and Inagaki, F., 1988a, Tertiary structure of mouse epidermal growth factor, J. Biochem. (Tokyo) 103:741–743.

    CAS  Google Scholar 

  • Kohda, D., Kodama, C., Kase, R., Nomoto, H., Hayashi, K., and Inagaki, F., 1988b, A comparative 1H NMR study of mouse α(l-53) and β(2-53) epidermal growth factors, Biochem. Int. 16:647–654.

    PubMed  CAS  Google Scholar 

  • Kohda, D., Shimada, I., Miyake, T., Fuwa, T., and Inagaki, F., 1989, Polypeptide chain fold of human transforming growth factor alpha analogous to those of mouse and human epidermal growth factors as studied by two-dimensional lH NMR, Biochemistry 28: 953–958.

    PubMed  CAS  Google Scholar 

  • Kohda, D., Sawada, T., and Inagaki, F., 1991, Characterization of pH titration shifts for all the nonlabile proton resonances in a protein by two-dimensional NMR: The case of mouse epidermal growth factor, Biochemistry 30:4896–4900.

    PubMed  CAS  Google Scholar 

  • Koide, H., Muto, Y., Kasai, H., Hoshi, K., Takusari, H., Kohri, K., Takahashi, S., Sasaki, T., Tsukomo, K., Miyake, T., Fuwa, T., Miyazawa, T., and Yokoyama, S., 1992, Recognition of an antiparallel β-sheet structure of human epidermal growth factor by its receptor. Site-directed mutagenesis studies, FEBS Lett. 302:39–42.

    PubMed  CAS  Google Scholar 

  • Kuntz, I. D., Thomason, J. F., and Oshiro, C. M., 1989, Distance geometry, Methods Enzymol. 177:159–204.

    PubMed  CAS  Google Scholar 

  • LeMaster, D. M., Deuteration in protein proton magnetic resonance, Methods EnzymoL 177:23-43.

    Google Scholar 

  • London, R. E., Perlman, M. E., and Davis, D. G., 1992, Relaxation-matrix analysis of the transferred nuclear Overhauser effect for finite exchange rates, J. Magn. Reson. 97:79–98.

    CAS  Google Scholar 

  • Makino, K., Morimoto, M., Nishi, M., Sakamoto, S., Tamura, A., Inooka, H., and Akasaka, K., 1987, Proton nuclear magnetic resonance study on the solution conformation of human epidermal growth factor, Proc. Natl. Acad. Sci. USA 84:7841–7845.

    PubMed  CAS  Google Scholar 

  • Marion, D., and Wüthrich, K., 1983, Application of phase sensitive two-dimensional correlated spectroscopy (COSY) for measurements of 1H-1H spin-spin coupling constants in proteins, Biochem. Biophys. Res. Commun. 113:967–974.

    PubMed  CAS  Google Scholar 

  • Marion, D., Driscoll, P. C., Kay, L. E., Wingfield, P. T., Bax, A., Gronenborn, A. M., and Clore, G. M., 1989, Overcoming the overlap problem in the assignment of lH NMR spectra of larger proteins by use of three-dimensional heteronuclear 1H-15N Hartmann-Hahn-multiple quantum coherence and nuclear overhauser-multiple quantum coherence spectroscopy: Application to interleukin 1β, Biochemistry 28:6150–6156.

    PubMed  CAS  Google Scholar 

  • Matsunami, R. K., Yette, M. L., Stevens, A., and Niyogi, S. K., 1991, Mutational analysis of leucine 47 in human epidermal growth factor, J. Cell. Biochem. 46:242–249.

    PubMed  CAS  Google Scholar 

  • Matthews, S. J., and Leatherbarrow, R. J., 1993, The use of osmolytes to facilitate protein NMR spectroscopy, J. Biomol. NMR 3:597–600.

    CAS  Google Scholar 

  • Mayo, K. H., 1984, Epidermal growth factor from the mouse. Structural characterization by proton nuclear magnetic resonance and nuclear overhauser experiments at 500 MHz, Biochemistry 23:3960–3973.

    PubMed  CAS  Google Scholar 

  • Mayo, K. H., 1985, Epidermal growth factor from the mouse. Physical evidence for a tiered beta-sheet domain: Two-dimensional NMR correlated spectroscopy and nuclear overhauser experiments on backbone amide protons, Biochemistry 24:3783–3794.

    PubMed  CAS  Google Scholar 

  • Mayo, K. H., and Burke, C., 1987, Structural and dynamical comparison of alpha-, beta-, and gamma-forms of murine epidermal growth factor, Eur. J. Biochem. 169:201–207.

    PubMed  CAS  Google Scholar 

  • Mayo, K. H., Schaudies, P., Savage, C. R., De Marco, A., and Kaptein, R., 1986a, Structural characterization and exposure of aromatic residues in epidermal growth factor from rat, Biochem. J. 239:13–18.

    PubMed  CAS  Google Scholar 

  • Mayo, K. H., DeMarco, A., and Kaptein, R., 1986b, Photo-CIDNP nuclear magnetic resonance as a probe for conformational changes in epidermal growth factor, Biochim. Biophys. Acta 874:181–186.

    PubMed  CAS  Google Scholar 

  • Mayo, K. H., DeMarco, A., Menegatti, E., and Kaptein, R., 1987, Interaction of epidermal growth factor with micelles monitored by photochemically induced dynamic nuclear polarization-1H NMR spectroscopy, J. Biol. Chem. 262:14899–14904.

    PubMed  CAS  Google Scholar 

  • Mayo, K. H., Cavalli, R. C., Peters, A. R., Boelens, R., and Kaptein, R., 1989, Sequencespecific lH NMR assignments and peptide backbone conformation in rat epidermal growth factor, Biochem. J. 257:197–205.

    PubMed  CAS  Google Scholar 

  • McCammon, J. A., 1987, Computer-aided molecular design, Science 238:486–491.

    PubMed  CAS  Google Scholar 

  • McCammon, J. A., and Harvey, S. C., 1987, Dynamics of Proteins and Nucleic Acids, Cambridge University Press, Cambridge.

    Google Scholar 

  • Menegatti, E., Scalia, A., Bortolotti, F., Ascenzi, P., and De Marco, A., 1989, Controlled proteolysis of mouse epidermal growth factor. An RP-HPLC and 1H NMR study, Int. J. Peptide Protein Res. 34:161–165.

    CAS  Google Scholar 

  • Metzler, W. J., Hare, D. R., and Pardi, A., 1989, Limited sampling of conformational space by the distance geometry algorithm: Implications for structures generated from NMR data, Biochemistry 28:7045–7052.

    PubMed  CAS  Google Scholar 

  • Mirau, P., 1988, Quantitative interpretation of a single NOESY spectrum, J. Magn. Reson. 80:439–447.

    CAS  Google Scholar 

  • Montelione, G. T., Wüthrich, K., Nice, E. C., Burgess, A. W., and Scheraga, H. A., 1986, Identification of two anti-parallel beta-sheet conformation in the solution structure of murine epidermal growth factor by proton magnetic resonance, Proc. Natl. Acad. Sci. USA 83:8594–8598.

    PubMed  CAS  Google Scholar 

  • Montelione, G. T., Wüthrich, K., Nice, E. C., Burgess, A. W., and Scheraga, H. A., 1987, Solution structure of murine epidermal growth factor: Determination of the polypep-tide backbone chain-fold by NMR and distance geometry, Proc. Natl. Acad. Sci. USA 84:5226–5230.

    PubMed  CAS  Google Scholar 

  • Montelione, G. T., Wüthrich, K., and Scheraga, H. A., 1988, Sequence-specific lH NMR assignments and identification of slowly exchanging amide protons in murine epidermal growth factor, Biochemistry 27:2235–2243.

    PubMed  CAS  Google Scholar 

  • Montelione, G. T., Winkler, M. E., Rauenbeller, P., and Wagner, G., 1989, Accurate measurements of long-range heteronuclear coupling constants from 2D NMR spectra of isotope-enriched proteins, J. Magn. Reson. 82:198–204.

    CAS  Google Scholar 

  • Montelione, G. T., Wüthrich, K., Burgess, A. W., Nice, E. C., Wagner, G., Gibson, K. D., and Scheraga, H. A., 1992, Solution structure of murine epidermal growth factor determined by NMR spectroscopy and refined by energy minimization with restraints, Biochemistry 31:236–249.

    PubMed  CAS  Google Scholar 

  • Moy, F. J., Scheraga, H. A., Liu, J.-F., Wu, R., and Montelione, G. T., 1989, Conformational characterization of a single-site mutant of murine epidermal growth factor (EGF) by 1H NMR provides evidence that leucine-47 is involved in the interactions with the EGF receptor, Proc. Natl. Acad. Sci. USA 86:9836–9840.

    PubMed  CAS  Google Scholar 

  • Mutsaers, J. H. G. M., Kamerling, J. P., Devos, R., Guisez, Y., Fiers, W., and Vliegenthart, J. F. G., 1986, Structural studies of the carbohydrate chains of human 7-interferon, Eur. J. Biochem. 156:651–654.

    PubMed  CAS  Google Scholar 

  • Nilges, M., Clore, G. M., and Gronenborn, A. M., 1988a, Determination of three-dimensional structures of proteins from interproton distance data by hybrid distance geometry-dynamical simulated annealing calculations, FEBS Lett. 228:317–324.

    Google Scholar 

  • Nilges, M., Clore, G. M., and Gronenborn, A. M., 1988b, Determination of three-dimensional structures of proteins from interproton distance data by dynamical simulated annealing from a random array of atoms, FEBS Lett. 239:129–136.

    PubMed  CAS  Google Scholar 

  • Nishimura, C., Hanzawa, H., Itoh, S., Yasukawa, K., Shimada, I., Kishimoto, T., and Arata, Y., 1990, Proton nuclear magnetic resonance study of interleukin-6: Chemical modifications and partial spectral assignments for the aromatic residues, Biochim. Biophys. Acta 1041:243–249.

    PubMed  CAS  Google Scholar 

  • Nishimura, C., Ekida, T., Masuda, S., Futatsugi, K., Itoh, S., Yasukawa, K., Kishimoto, T., and Arata, Y., 1991, Chemical modification and 1H NMR studies on the receptor binding region of human interleukin-6, Eur. J. Biochem. 196:377–384.

    PubMed  CAS  Google Scholar 

  • Olejniczak, E. T., Poulsen, F. M., and Dobson, C. M., 1984, Distance dependence of proton nuclear overhauser effects in proteins, J. Magn. Reson. 59:518–523.

    CAS  Google Scholar 

  • Olejniczak, E. T., Xu, R. X., and Fesik, S. W., 1992a, A 4D HCCH-TOCSY experiment for assigning the side chain lH and 13C resonances of proteins, J. Biomol. NMR 2:655–659.

    PubMed  CAS  Google Scholar 

  • Olejniczak, E. T., Xu, R. X., Petros, A. M., and Fesik, S. W., 1992b, Optimized constant-time 4D HNCAHA and HN(CO)CAHA experiments. Applications to the backbone assignments of the FKBP/ascomycin complex, J. Magn. Reson. 100:444–450.

    CAS  Google Scholar 

  • Oschkinat, H., Griesinger, C., Krautlis, P. J., Sørensen, O. W., Ernst, R. R., Gronenborn, A. M., and Clore, G. M., 1988, Three-dimensional NMR spectroscopy of a protein in solution, Nature 332:374–376.

    PubMed  CAS  Google Scholar 

  • Oshiro, C. M., Thomason, J., and Kuntz, I. D., 1991, Effects of limited input distance constraints upon the distance geometry algorithm, Biopolymers 31:1049–1064.

    PubMed  CAS  Google Scholar 

  • Palmieri, R., Lee, R. W.-K., and Dunn, M. F., 1988, lH Fourier transform NMR studies of insulin: Coordination of calcium to the Glu(B13) site drives hexamer assembly and induces a conformational change, Biochemistry 27:3387–3397.

    PubMed  CAS  Google Scholar 

  • Piotto, M., Saudek, V., and Sklenár, V., 1992, Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions, J. Biomol. NMR 2:661–665.

    PubMed  CAS  Google Scholar 

  • Powers, R., Garrett, D. S., March, C. J., Frieden, E. A., Gronenborn, A. M., and Clore, G. M., 1992a, 1H, 15N, 13C., and 13CO assignments of human interleukin-4 using three-dimensional double-and triple-resonance heteronuclear magnetic resonance spectroscopy, Biochemistry 31:4334–4346.

    PubMed  CAS  Google Scholar 

  • Powers, R., Garrett, D. S., March, C. J., Frieden, E. A., Gronenborn, A. M., and Clore, G. M., 1992b, Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy, Science 256:1673–1677.

    PubMed  CAS  Google Scholar 

  • Priestle, J. P., Schär, H.-P, and Grütter, M. G., 1988, Crystal structure of the cytokine interleukin-lβ, EMBO J. 7:339–343.

    PubMed  CAS  Google Scholar 

  • Priestle, J. P., Schär, H. P., and Grutter, M. G., 1989, Crystallographic refinement of interleukin 1β at 2.0 Å resolution, Proc. Natl. Acad. Sci. USA 86:9667–9671.

    PubMed  CAS  Google Scholar 

  • Ramhesh, V., and Bradbury, J. H., 1986, 1H NMR studies of insulin, Int. J. Pept. Protein Res. 28:146–153.

    Google Scholar 

  • Rance, M., Sørensen, O. W., Bodenhausen, G., Wagner, G., Ernst, R. R., and Wüthrich, K., 1983, Improved spectral resolution in COSY lH NMR spectra of proteins via double quantum filtering, Biochem. Biophys. Res. Commun. 117:479–485.

    PubMed  CAS  Google Scholar 

  • Redfield, C., Smith, L. J., Boyd, J., Lawrence, G. M. P., Edwards, R. G., Smith, R. A. G., and Dobson, C. M., 1991, Secondary structure and topology of human interleukin-4 in solution, Biochemistry 30:11029–11035.

    PubMed  CAS  Google Scholar 

  • Redfield, C., Boyd, J., Smith, L. J., Smith, R. A. G., and Dobson, C. M., 1992, Loop mobility in a four-helix bundle protein: 15N NMR relaxation measurements on human interleukin-4, Biochemistry 31:10431–10437.

    PubMed  CAS  Google Scholar 

  • Richardson, J. M., Clowes, R. T., Boucher, W., Domaille, P. J., Hardman, C. H., Keeler, J., and Laue, E. D., 1993, The use of heteronuclear cross polarization to enhance the sensitivity of triple-resonance NMR experiments. Improved 4D HCCNNH pulse sequences, J. Magn. Reson. Ser. B 101:223–227.

    CAS  Google Scholar 

  • Sato, A., Nishimura, S., Ohkubo, T., Kyogoku, Y., Koyama, S., Kobayashi, M., Yasuda, T., and Kobayashi, Y., 1992, lH NMR assignment and secondary structure of human insulin-like growth factor-I (IGF-I) in solution, J. Biochem. (Tokyo) 111:529–536.

    CAS  Google Scholar 

  • Satoh, T., Nakamura, S., Taga, T., Matsuda, T., Hirano, T., Kishimoto, T., and Kaziro, Y, 1988, Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6, Mol. Cell. Biol. 8:3546–3549.

    PubMed  CAS  Google Scholar 

  • Scheek, R. M., van Gunsteren, W. F., and Kaptein, R., 1989, Molecular dynamics simulation techniques for determination of molecular structures from nuclear magnetic resonance data, Methods Enzymol. 177:204–218.

    PubMed  CAS  Google Scholar 

  • Schmieder, P., Thanabal, V., Mclntosh, L. P., Dahlquist, F. W., and Wagner, G., 1991, Measurements of Ha-HN vicinal coupling constants in a protein with large linewidths in a new 3D 1H-15N-13C quadruple resonance NMR experiment, J. Am. Chem. Soc. 113:6323–6324.

    CAS  Google Scholar 

  • Shaka, A. J., and Freeman, R., 1983, Simplification of NMR spectra by filtration through multiple-quantum coherence, J. Magn. Reson. 51:169–173.

    CAS  Google Scholar 

  • Smith, L. J., Redfield, C., Boyd, J., Lawrence, G. M. P., Edwards, R. G., Smith, R. A. G., and Dobson, C. M., 1992, Human interleukin-4. The solution structure of a four-helix bundle protein, J. Mol. Biol. 224:899–904.

    PubMed  CAS  Google Scholar 

  • Sorensen, P., and Poulsen, F., 1992, A simple and economical algal culture system for stable isotopic labelling, J. Biomol. NMR 2:99–101.

    Google Scholar 

  • Stockman, B. J., Scahill, T. A., Roy, M., Ulrich, E. L., Strakalaitis, N. A., Brunner, D. P., Yem, A. W., and Deibel, M. R., Jr., 1992, Secondary structure and topology of interleukin-1 receptor antagonist protein determined by heteronuclear three-dimensional NMR spectroscopy, Biochemistry 31:5237–5245.

    PubMed  CAS  Google Scholar 

  • Syperski, T., Wider, G., Bushweller, J. H., and Wüthrich, K., 1993, 3D 13C-15N heteronuclear two-spin coherence spectroscopy for polypeptide backbone assignments in 13C-15N double-labeled proteins, J. Biomol NMR 3:127–132.

    Google Scholar 

  • Vercelli, D., Jabara, H. H., Arai, K., Yokota, T., and Geha, R. S., 1989, Endogenous interleukin 6 plays an obligatory role in interleukin 4-dependent human Ige synthesis, Eur. J. Immunol 19: 1419–1424.

    PubMed  CAS  Google Scholar 

  • Vuister, G. W., Boelens, R., and Kaptein, R., 1988, Nonselective three-dimensional NMR spectroscopy. The 3D NOE-HOHAHA experiment, J. Magn. Reson, 80:176–185.

    CAS  Google Scholar 

  • Vuister, G. W., Boelens, R., Padilla, A., and Kaptein, R., 1991, Statistical analysis of double NOE transfer pathways in proteins as measured in 3D NOE-NOE spectroscopy, J. Biomol. NMR 1:421–438.

    PubMed  CAS  Google Scholar 

  • Vuister, G. W., Boelens, R., Kaptein, R., Burgering, M., and van Zijl, P. C. M., 1992, Gradient-enhanced 3D NOESY-HMQC spectroscopy, J. Biomol NMR 2:301–305.

    CAS  Google Scholar 

  • Wagner, G., 1993, Prospects for NMR of large proteins, J. Biomol NMR 3:375–385.

    PubMed  CAS  Google Scholar 

  • Wagner, G., Hyberts, S. G., and Havel, T. F., 1992, NMR structure determination in solution: A critique and comparison with X-ray crystallography, Annu. Rev. Biophys. Biomol Struct. 21:167–198.

    PubMed  CAS  Google Scholar 

  • Walter, M. R., Cook, W. J., Ealick, S. E., Nagabhushan, T. L., Trotta, P. P., and Bugg, C. E., 1992, Three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor, J. Mol. Biol. 224:1075–1085.

    PubMed  CAS  Google Scholar 

  • Weisemann, R., Rüterjans, H., and Bermel, B., 1993, 3D triple-resonance NMR techniques for the sequential assignment of NH and 15N resonances in 15N-and 13C-labelled proteins, J. Biomol NMR 3:113–120.

    PubMed  CAS  Google Scholar 

  • Weiss, M. A., Nguyen, D. T., Khait, I., Inouye, K., Frank, B. H., Beckage, M., O’Shea, E., Shoelson, S. E., Karplus, M., and Neuringer, L. J., 1989, Two-dimensional NMR and photo-CIDNP studies of the insulin monomer: Assignment of aromatic resonances with application to protein folding, structure, and dynamics, Biochemistry 28:9855–9873.

    PubMed  CAS  Google Scholar 

  • Wider, G., Macura, S., Kumar, A., Ernst, R. R., and Wüthrich, K., 1984, Homonuclear two-dimensional 1H NMR of proteins. Experimental procedures, J. Magn. Reson. 56: 207–234.

    CAS  Google Scholar 

  • Wilkinson, A. J., Cooke, R. M., Pastore, A., Campbell, I. D., Sheard, B., and Gregory, H., 1987, The determination of the three-dimensional structure of human epidermal growth factor from 1H NMR data, Protides Biol. Fluids 35:453–456.

    CAS  Google Scholar 

  • Williamson, M. P., and Madison, V. S., 1990, Three-dimensional structure of porcine C5a desArg from 1H nuclear magnetic resonance data, Biochemistry 29:2895–2905.

    PubMed  CAS  Google Scholar 

  • Wingfield, P., Graber, P., Movva, N. R., Gronenborn, A. M., and MacDonald, H. R., 1987, N-terminal-methionylated interleukin-lβ has reduced receptor-binding affinity, FEBS Lett. 215:160–164.

    PubMed  CAS  Google Scholar 

  • Wingfield, P., Graber, P., Shaw, A. R., Gronenborn, A. M., Clore, G. M., and MacDonald, H. R., 1989, Preparation, characterization and application of interleukin-lβ mutant proteins with surface-accessible cysteine residues, Eur. J. Biochem. 179:565–571.

    PubMed  CAS  Google Scholar 

  • Wittekind, M., and Mueller, L., 1993, HNCACB, a high-sensitivity 3D NMR experiment to correlate amide-proton and nitrogen resonances with the alpha-and beta-carbon resonances in proteins, J. Magn. Reson. Sen B 101:201–205.

    CAS  Google Scholar 

  • Wokaun, A., and Ernst, R. R., 1977, Selective detection of multiple-quantum transitions in NMR by two-dimensional spectroscopy, Chem. Phys. Lett. 52:407–412.

    CAS  Google Scholar 

  • Wüthrich, K., 1986, NMR of Proteins and Nucleic Acids, John Wiley and Sons, New York.

    Google Scholar 

  • Wüthrich, K., 1989a, Protein structure determination in solution by nuclear magnetic resonance spectroscopy, Science 243:45–50.

    PubMed  Google Scholar 

  • Wüthrich, K., 1989b, Determination of three-dimensional protein structures in solution by nuclear magnetic resonance: An overview, Methods Enzymol. 177:125–131.

    PubMed  Google Scholar 

  • Wüthrich, K., 1990, Protein structure determination in solution by NMR spectroscopy, J. Biol. Chem. 265:22059–22062.

    PubMed  Google Scholar 

  • Wüthrich, K., Billeter, M., and Braun, W., 1984, Polypeptide secondary structure determination by NMR observation of short proton-proton distances, J. Mol. Biol. 180:715–740.

    PubMed  Google Scholar 

  • Yamamoto, S., Hase, S., Fukuda, S., Sano, O., and Ikenaka, T, 1989, Structures of the sugar chains of interferon-γ produced by human myelomonocyte cell line HBL-38, J. Biochem. (Tokyo) 105:547–555.

    CAS  Google Scholar 

  • Zuiderweg, E. R. P., Nettesheim, D. G., Mollison, K. W., and Carter, G. W., 1989, Tertiary structure of human complement C5a in solution from nuclear magnetic resonance data, Biochemistry 28:172–185.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. NMR Laboratory, University of Kansas, Lawrence, Kansas, 66045, USA

    David G. Vander Velde

  2. School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado, 80262, USA

    James Matsuura & Mark C. Manning

Authors
  1. David G. Vander Velde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark C. Manning
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Utah, Salt Lake City, Utah, USA

    James N. Herron

  2. National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands

    Wim Jiskoot

  3. Groningen-Utrecht Institute for Drug Exploration, Utrecht University, and Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands

    Daan J. A. Crommelin

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Velde, D.G.V., Matsuura, J., Manning, M.C. (1995). Two-, Three-, and Four-Dimensional Nuclear Magnetic Resonance Spectroscopy of Protein Pharmaceuticals. In: Herron, J.N., Jiskoot, W., Crommelin, D.J.A. (eds) Physical Methods to Characterize Pharmaceutical Proteins. Pharmaceutical Biotechnology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1079-0_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-1079-0_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1081-3

  • Online ISBN: 978-1-4899-1079-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation