Solution of a Protein Crystal Structure with a Model Obtained from NMR Interproton Distance Restraints

Model calculations were performed to test the possibility of solving crystal structures of proteins by Patterson search techniques with three-dimensional structures obtained from nuclear magnetic resonance (NMR) interproton distance restraints. Structures for crambin obtained from simulated NMR data were used as the test system; the root-mean-square deviations of the NMR structures from the x-ray structure were 1.5 to 2.2 � for backbone atoms and 2.0 to 2.8 � for side-chain atoms. Patterson searches were made to determine the orientation and position of the NMR structures in the unit cell. The correct solution was obtained by comparing the rotation function results of several of the NMR structures and the average structure derived from them. Conventional refinement techniques reduced the R factor from 0.43 at 4 � resolution to 0.27 at 2 � resolution without inclusion of water molecules. The partially refined structure has root-mean-square backbone and side-chain atom deviations from the x-ray structure of 0.5 and 1.3 �, respectively.

[1]  W. Hendrickson.  Stereochemically restrained refinement of macromolecular structures. , 1985, Methods in enzymology.

[2]  Kurt Wüthrich,et al.  Secondary structure of the α-amylase polypeptide inhibitor Tendamistat from Streptomyces tendae determined in solution by 1H nuclear magnetic resonance , 1985 .

[3]  Timothy F. Havel,et al.  An evaluation of the combined use of nuclear magnetic resonance and distance geometry for the determination of protein conformations in solution. , 1985, Journal of molecular biology.

[4]  N Go,et al.  Calculation of protein conformations by proton-proton distance constraints. A new efficient algorithm. , 1985, Journal of molecular biology.

[5]  R. Huber,et al.  Crystal structure determination, refinement and the molecular model of the alpha-amylase inhibitor Hoe-467A. , 1986, Journal of molecular biology.

[6]  Wayne A. Hendrickson,et al.  Structure of the hydrophobic protein crambin determined directly from the anomalous scattering of sulphur , 1981, Nature.

[7]  M Karplus,et al.  Application of molecular dynamics with interproton distance restraints to three-dimensional protein structure determination. A model study of crambin. , 1986, Journal of molecular biology.

[8]  K Wüthrich,et al.  Studies by 1H nuclear magnetic resonance and distance geometry of the solution conformation of the alpha-amylase inhibitor tendamistat. , 1986, Journal of molecular biology.

[9]  M. Teeter,et al.  Water structure of a hydrophobic protein at atomic resolution: Pentagon rings of water molecules in crystals of crambin. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Huber,et al.  A group refinement procedure in protein crystallography using Fourier transforms , 1985 .

[11]  J. Hartsuck,et al.  Rotation‐function space groups , 1980 .

[12]  G. Clore,et al.  Nuclear magnetic resonance study of the globular domain of chicken histone H5: resonance assignment and secondary structure. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M Karplus,et al.  Three-dimensional structure of proteins determined by molecular dynamics with interproton distance restraints: application to crambin. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Karplus,et al.  Crystallographic R Factor Refinement by Molecular Dynamics , 1987, Science.

[15]  W F van Gunsteren,et al.  A protein structure from nuclear magnetic resonance data. lac repressor headpiece. , 1985, Journal of molecular biology.

[16]  R. Wells,et al.  Isolation of an olfactory cDNA: similarity to retinol-binding protein suggests a role in olfaction. , 1987, Science.

[17]  R. R. Ernst,et al.  Two‐dimensional spectroscopy. Application to nuclear magnetic resonance , 1976 .

[18]  Eaton E. Lattman,et al.  Use of the rotation and translation functions , 1985 .

[19]  W. Kabsch.  A solution for the best rotation to relate two sets of vectors , 1976 .

[20]  R. A. Crowther,et al.  A method of positioning a known molecule in an unknown crystal structure , 1967 .

[21]  Richard R. Ernst,et al.  Investigation of exchange processes by two‐dimensional NMR spectroscopy , 1979 .