Protein Structure and Engineering pp 69-78 | Cite as

# NMR Method for Protein Structure Determination in Solution

## Abstract

The introduction of Nuclear Magnetic Resonance as a second method for protein structure determination, besides X-ray diffraction in single crystals, has already helped to significantly increase the number of known protein structures. However, it is also of more fundamental interest, since it provides data that are in many ways complementary to those obtained from X-ray crystallography. Its use thus promises to widen our view of protein molecules with regard to a better grasp of the relations between structure and function. The complementarity of the two methods results from the facts that the time scales of the two types of measurements are widely different, and that, in contrast to the need of single crystals for diffraction studies, the NMR measurements use proteins in solution or other noncrystalline states.

## Keywords

Nuclear Magnetic Resonance Root Mean Square Deviation Resonance Assignment Distance Geometry Protein Structure Determination## Preview

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## References

- Anil-Kumar, Wagner, G., Ernst, R.R. and Wüthrich, K., 1980, Studies of J-connectivities and selective
^{1}H-^{1}H Overhauser effects in H_{2}O solutions of biological macromolecules by two-dimensional NMR experiments,*Biochem. Biophys. Res. Comm.*96:1156.Google Scholar - Arseniev, A., Schultze, P., Wörgötter, E., Braun, W., Wagner, G., Vasák, M., Kägi, J.H.R. and Wüthrich, K., 1988, Three-dimensional structure of rabbit liver [Cd
^{7}]-metallothionein-2a in aqueous solution determined by nuclear magnetic resonance,*J. Mol. Biol.*201:637.CrossRefGoogle Scholar - Aue, W.P., Bartholdi, E. and Ernst, R.R., 1976, Two-dimensional spectroscopy: application to NMR,
*J. Chem. Phys.*64:2229.ADSCrossRefGoogle Scholar - Billeter, M., Braun, W. and Wüthrich, K., 1982, Sequential resonance assignments in protein
^{1}H nuclear magnetic resonance spectra, computation of sterically allowed proton-proton distances and statistical analysis of proton-proton distances in single crystal protein conformations,*J. Mol. Biol.*155:321.CrossRefGoogle Scholar - Billeter, M., Basus, V.J. and Kuntz, I.D., 1988, A program for semi-automatic sequential resonance assignments in protein
^{1}H nuclear magnetic resonance spectra,*J. Magn. Res.*76:400.Google Scholar - Billeter, M., Havel, T.F. and Wüthrich, K., 1987, The ellipsoid algorithm as a method for the determination of polypeptide conformations from experimental distance constraints and energy minimization,
*J. Comp. Chem.*8:132.CrossRefGoogle Scholar - Billeter, M., Schaumann, Th., Braun, W. and Wüthrich, K., 1989a, Restrained energy refinement with two different algorithms and force fields of the structure of the oc-amylase inhibitor Tendamistat determined by NMR in solution,
*Biopolymers*, in press.Google Scholar - Billeter, M., Kline, A.D., Braun, W., Huber, R. and Wüthrich, K., 1989b, Comparison of the high-resolution structures of the α-amylase inhibitor Tendamistat determined by NMR in solution and by X-ray diffraction in single crystals,
*J. Mol. Biol.*206:677.CrossRefGoogle Scholar - Blumenthal, L.M., 1970, “Theory and application of distance geometry,” Chelsea, New York.Google Scholar
- Blundell, T.L. and Johnson, L.N., 1976, “Protein crystallography,” Academic Press, New York.Google Scholar
- Braun, W., 1987, Distance geometry and related methods for protein structure determination from NMR data,
*Quart. Rev. Biophys.*19:115.CrossRefGoogle Scholar - Braun, W. and Go, N., 1985, Calculation of protein conformations by proton-proton distance constraints, a new efficient algorithm,
*J. Mol. Biol.*186:611.CrossRefGoogle Scholar - Braun, W., Bosch, C., Brown, L.R., Go, N. and Wüthrich, K., 1981, Combined use of proton-proton Overhauser enhancements and a distance geometry algorithm for determination of polypeptide conformations. Application to micelle-bound glucagon,
*Biochim. Biophys. Acta*667:377.CrossRefGoogle Scholar - Braun, W., Wider, G., Lee, K.H. and Wüthrich, K., 1983, Conformation of glucagon in a lipid-water interphase by
^{1}H nuclear magnetic resonance,*J. Mol. Biol.*169:921.CrossRefGoogle Scholar - Brünger, A.T., Clore, G.M., Gronenborn, A.M. and Karplus, M., 1986, Three-dimensional structure of proteins determined by molecular dynamics with interproton distance restraints: Application to crambin,
*Proc. Natl. Acad. Sci. USA*83:3801.ADSCrossRefGoogle Scholar - Clore, G.M., Gronenborn, A.M., James, M.N.G., Kjaer, M., McPhalen, C.A. and Poulsen, F.M., 1987, Comparison of the solution and X-ray structures of barley serine proteinase inhibitor-2,
*Protein Engineering*1:313.CrossRefGoogle Scholar - Crippen, G.M. and Havel, T., 1988, “Distance geometry and molecular conformation,” Wiley, New York.MATHGoogle Scholar
- Driscoll, P.C., Gronenborn, A.M. and Clore, G.M., 1989, The influence of stereospecific assignments on the determination of three-dimensional structures of proteins by NMR spectroscopy. Application to the sea anemone protein BDS-I,
*FEBS Lett.*243:223.CrossRefGoogle Scholar - Dubs, A., Wagner, G. and Wüthrich, K., 1979, Individual assignments of amide proton resonances in the proton NMR spectrum of the basic pancreatic trypsin inhibitor,
*Biochim. Biophys. Acta*577:177.CrossRefGoogle Scholar - Duncan, B., Buchanan, B.G., Hayes-Roth, B., Lichtarge, O., Altman, R., Brinkley, J., Hewett, M., Cornelius, C. and Jardetzky, O., 1987, PROTEAN: A new method for deriving solution structures of proteins,
*Bull. Magn. Reson.*8:111.Google Scholar - Englander, S.W. and Wand, A.J., 1987, Main-chain-directed strategy for the assignment of
^{1}H NMR spectra of proteins,*Biochemistry*26:5953.CrossRefGoogle Scholar - Ernst, R.R., Bodenhausen, G., Wokaun, A., 1987, “Principles of nuclear magnetic resonance in one and two dimensions,” Clarendon Press, Oxford.Google Scholar
- Fesik, S.W., Gampe, R.T., Jr., Zuiderweg, E.R.P., Kohlbrenner, W.E. and Weigl, D., 1989, Heteronuclear three-dimensional NMR spectroscopy applied to CMP-KDO synthetase (27.5 kD),
*Biochem. Biophys. Res. Comm.*159:842.CrossRefGoogle Scholar - Furey, W.F., Robbins, A.H., Clancy, L.L., Winge, D.R., Wang, B.C. and Stout, C.D., 1986, Crystal structure of Cd, Zn metallothionein,
*Science*231:704.ADSCrossRefGoogle Scholar - Gordon, S.L. and Wüthrich, K., 1978, Transient proton-proton Overhauser effects in horse ferrocytochrome c,
*J. Amer. Chem. Soc.*100:7094.CrossRefGoogle Scholar - Griffey, R.H. and Redfield, A.G., 1987, Proton-detected heteronuclear edited and correlated nuclear magnetic resonance and nuclear Overhauser effect in solution,
*Quart. Rev. Biophys.*19:51.CrossRefGoogle Scholar - Griffey, R.H., Redfield, A.G., Mcintosh, L.P., Oas, T.G. and Dahlquist, F.W., 1986, Assignment of proton amide resonances of T4 lysozyme by
^{13}C and^{15}N multiple isotopic labeling,*J. Amer. Chem. Soc.*108:6816.CrossRefGoogle Scholar - Güntert, P., Braun, W., Billeter, M. and Wüthrich, K., 1989, Automated stereospecific
^{1}H*-*NMR assignments and their impact on the precision of protein structure determinations in solution,*J. Amer. Chem. Soc.*111:3997.CrossRefGoogle Scholar - Havel, T.F. 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
^{1}H-^{1}H proximities in solution,*Bull. Math. Biol.*46:673.MATHGoogle Scholar - Hendrickson, W.A. and Konnert, J.H., 1981, Stereochemically restrained crystallographic least-squares refinement of macromolecular structures,
*in:*“Biomolecular Structure, Conformation, Function and Evolution,” Voll, R. Srinivasan, N. Yathindra and E. Subramanian, eds., Pergamon Press, New York.Google Scholar - Hyberts, S.G., Märki, W. and Wagner, G., 1987, Stereospecific assignments of side-chain protons and characterization of torsion angles in eglin c,
*Eur. J. Biochem.*164:625.CrossRefGoogle Scholar - Kaptein, R., Boelens, R., Scheek, R.M. and van Gunsteren, W.F., 1988, Protein Structures from NMR,
*Biochemistry*27:5389.CrossRefGoogle Scholar - Kline, A.D., Braun, W. and Wüthrich, K., 1986, Studies by
^{1}H nuclear magnetic resonance and distance geometry of the solution conformation of the a-amylase inhibitor Tendamistat,*J. Mol Biol*189:377.CrossRefGoogle Scholar - Kline, A.D., Braun, W. and Wüthrich, K., 1988, Determination of the complete three-dimensional structure of the a-amylase inhibitor Tendamistat in aqueous solution by nuclear magnetic resonance and distance geometry,
*J. Mol Biol*204:675.CrossRefGoogle Scholar - LeMaster, D.M. and Richards, F.M., 1985,
^{1}H–^{15}N heteronuclear NMR studies of*Escherichia coli*thioredoxin in samples isotopically labeled by residue type,*Biochemistry*24:7263.CrossRefGoogle Scholar - LeMaster, D.M. and Richards, F.M., 1988, NMR sequential assignment of
*Escherichia coli*thioredoxin utilizing random fractional deuteration,*Biochemistry*27:142.CrossRefGoogle Scholar - Marion, D., Kay, L.E., Sparks, S.W., Torchia, D.A. and Bax, A., 1989, Three-dimensional heteronuclear NMR of
^{15}N-labeled proteins,*J. Amer. Chem. Soc.*111:1515.CrossRefGoogle Scholar - Markley, J.L., Putter, I. and Jardetzky, O., 1968, High-resolution nuclear magnetic resonance spectra of selectively deuterated staphylococcal nuclease,
*Science*161:1249.ADSCrossRefGoogle Scholar - Nagayama, K., Wüthrich, K., Bachmann, P. and Ernst, R.R., 1977, Two-dimensional J-resolved
^{1}H NMR spectroscopy of biological macromolecules,*Biochem. Biophys. Res. Comm.*78:99.CrossRefGoogle Scholar - Otting, G., Senn, H., Wagner, G. and Wüthrich, K., 1986, Editing of 2D
^{1}H NMR spectra using X half-filters. Combined use with residue-selective N labeling of proteins,*J. Magn. Res.*70:500.Google Scholar - Pflugrath, J.W., Wiegand, G., Huber, R. and Vértesy, L., 1986, Crystal structure determination, refinement and the molecular model of the a-amylase inhibitor HOE 467 A,
*J. Mol Biol*189:383.CrossRefGoogle Scholar - Sasaki, K., Dockevill, S., Ackmiak, D.A., Tickle, I.J. and Blundell, T.L., 1975, X-ray analysis of glucagon and its relationship to receptor binding,
*Nature*257:751.ADSCrossRefGoogle Scholar - Schultze, P., Wörgötter, E., Braun, W., Wagner, G., Vasák, M., Kägi, J.H.R. and Wüthrich, K., 1988, The conformation of [Cd
^{7}]-metallothionein-2 from rat liver in aqueous solution determined by nuclear magnetic resonance,*J. Mol Biol.*203:251.CrossRefGoogle Scholar - Senn, H., Billeter, M. and Wüthrich, K., 1984, The spatial structure of the axially bound methionine in solution conformations of horse ferrocytochrome c and Pseudomonas aeruginosa ferrocytochrome c-551 by
^{l}H NMR,*Eur. Biophys. J.*11:3.CrossRefGoogle Scholar - Senn, H., Otting, G. and Wüthrich, K., 1987, Protein structure and interactions by combined use of sequential NMR assignments and isotope labeling,
*J. Amer. Chem. Soc.*109:1090.CrossRefGoogle Scholar - Senn, H., Werner, B., Messerle, B.A., Weber, C., Traber, R. and Wüthrich, K., 1989, Stereospecific assignment of the methyl
^{1}H NMR lines of valine and leucine in polypeptides by nonrandom^{13}C labelling,*FEBS Lett.*249:113.CrossRefGoogle Scholar - Wagner, G. and Wüthrich, K., 1979, Truncated driven nuclear Overhauser effect (TOE), a new technique for studies of selective
^{1}H-^{1}H Overhauser effects in the presence of spin diffusion,*J. Magn. Reson.*33:675.Google Scholar - Wagner, G. and Wüthrich, K., 1982, Sequential resonance assignments in protein
^{1}H nuclear magnetic resonance spectra. Basic pancreatic trypsin inhibitor,*J. Mol Biol*155:347.CrossRefGoogle Scholar - Wagner, G., Braun, W., Havel, T.F., Schaumann, Th., Go, N. and Wüthrich, K., 1987, Protein structures in solution by nuclear magnetic resonance and distance geometry. The polypeptide fold of the basic pancreatic trypsin inhibitor determined using two different algorithms, DISGEO and DISMAN,
*J. Mol Biol.*196:611.CrossRefGoogle Scholar - Weber, P.L., Morrison, R. and Hare, D., 1988, Determining stereo-specific
^{1}H NMR assignments from distance geometry calculations,*J. Mol. Biol.*204:483.CrossRefGoogle Scholar - Weber, P.L. and Mueller, L., 1989, Use of
^{15}N labeling for automated three-dimensional sorting of cross peaks in protein 2D NMR spectra,*J. Magn. Res.*81:430.Google Scholar - Wider, G., Lee, K.H. and Wüthrich, K., 1982, Sequential resonance assignments in protein
^{1}H nuclear magnetic resonance spectra. Glucagon bound to perdeuterated dodecylphosphocholine micelles,*J. Mol. Biol.*155:367.CrossRefGoogle Scholar - Williamson, M.P., Havel, T.F. and Wüthrich, K., 1985, Solution conformation of the proteinase inhibitor HA from bull seminal plasma by
^{1}H nuclear magnetic resonance and distance geometry,*J. Mol. Biol.*182:295.CrossRefGoogle Scholar - Wörgötter, E., Wagner, G. and Wüthrich, K., 1986, Simplification of two-dimensional
^{1}H NMR spectra using an X-filter,*J. Amer. Chem. Soc.*108:6162.CrossRefGoogle Scholar - Wörgötter, E., Wagner, G., Vasák, M., Kägi, J.H.R. and Wüthrich, K., 1988, Heteronuclear filters for two-dimensional
^{1}H NMR. Identification of the metal-bound amino acids in metallothionein and observation of small heteronuclear long-range couplings,*J. Amer. Chem. Soc.*110:2388.CrossRefGoogle Scholar - Wüthrich, K., 1983, Sequential individual resonance assignments in the
^{1}H NMR spectra of polypeptides and proteins,*Biopolymers*22:131.CrossRefGoogle Scholar - Wüthrich, K., 1986, “NMR of proteins and nucleic acids,” Wiley, New York.Google Scholar
- Wüthrich, K., 1989a, The development of nuclear magnetic resonance spectroscopy as a technique for protein structure determination,
*Accts. Chem. Res.*22:36.CrossRefGoogle Scholar - Wüthrich, K., 1989b, Protein structure determination in solution by NMR spectroscopy,
*Science*243:45.ADSCrossRefGoogle Scholar - Wüthrich, K., Wider, G., Wagner, G. and Braun, W., 1982, Sequential resonance assignments as a basis for determination of spatial protein structures by high resolution proton nuclear magnetic resonance,
*J. Mol. Biol.*155:311.CrossRefGoogle Scholar - Wüthrich, K., Billeter, M. and Braun, W., 1983, Pseudo-structures for the 20 common amino acids for use in studies of protein conformations by measurements of intramolecular proton-proton distance constraints with nuclear magnetic resonance,
*J. Mol. Biol.*169:949.CrossRefGoogle Scholar - Wüthrich, K., Billeter, M. and Braun, W., 1984, Polypeptide secondary structure determination by nuclear magnetic resonance observation of short proton-proton distances,
*J. Mol. Biol.*180:715.CrossRefGoogle Scholar - Zuiderweg, E.R.P., Boelens, R. and Kaptein, R., 1985, Stereospecific assignments of
^{1}H-NMR methyl lines and conformation of valyl residues in the*lac*repressor headpiece,*Biopolymers*24:601.CrossRefGoogle Scholar