Structural basis of amino acid alpha helix propensity.

The propensity of an amino acid to form an alpha helix in a protein was determined by multiple amino substitutions at positions 44 and 131 in T4 lysozyme. These positions are solvent-exposed sites within the alpha helices that comprise, respectively, residues 39 to 50 and 126 to 134. Except for two acidic substitutions that may be involved in salt bridges, the changes in stability at the two sites agree well. The stability values also agree with those observed for corresponding amino acid substitutions in some model peptides. Thus, helix propensity values derived from model peptides can be applicable to proteins. Among the 20 naturally occurring amino acids, proline, glycine, and alanine each have a structurally unique feature that helps to explain their low or high helix propensities. For the remaining 17 amino acids, it appears that the side chain hydrophobic surface buried against the side of the helix contributes substantially to alpha helix propensity.

[1]  E. Stellwagen,et al.  Effect of central-residue replacements on the helical stability of a monomeric peptide. , 1990, Biochemistry.

[2]  B. Matthews,et al.  A mutant T4 lysozyme (Val 131 → Ala) designed to increase thermostability by the reduction of strain within an α‐helix , 1990, Proteins.

[3]  D. E. Anderson,et al.  Expression and nitrogen-15 labeling of proteins for proton and nitrogen-15 nuclear magnetic resonance. , 1989, Methods in enzymology.

[4]  R. B. Hermann.  Use of solvent cavity area and number of packed solvent molecules around a solute in regard to hydrocarbon solubilities and hydrophobic interactions. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Matthews,et al.  Structure and thermal stability of phage T4 lysozyme. , 1987, Methods in enzymology.

[6]  U. Sauer,et al.  Tolerance of T4 lysozyme to proline substitutions within the long interdomain alpha-helix illustrates the adaptability of proteins to potentially destabilizing lesions. , 1991, The Journal of biological chemistry.

[7]  A. Fersht,et al.  Alpha-helix stability in proteins. II. Factors that influence stability at an internal position. , 1992, Journal of molecular biology.

[8]  B. Matthews,et al.  Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. , 1992, Science.

[9]  B. Lee,et al.  The interpretation of protein structures: estimation of static accessibility. , 1971, Journal of molecular biology.

[10]  B. Matthews,et al.  An oscillation data collection system for high‐resolution protein crystallography , 1981 .

[11]  F. Eckstein,et al.  The rapid generation of oligonucleotide-directed mutations at high frequency using phosphorothioate-modified DNA. , 1985, Nucleic acids research.

[12]  K. Dill,et al.  Denatured states of proteins. , 1991, Annual review of biochemistry.

[13]  B. Matthews,et al.  Analysis of the effectiveness of proline substitutions and glycine replacements in increasing the stability of phage T4 lysozyme , 1992, Biopolymers.

[14]  Robert L. Baldwin,et al.  Relative helix-forming tendencies of nonpolar amino acids , 1990, Nature.

[15]  T. Kunkel.  Rapid and efficient site-specific mutagenesis without phenotypic selection. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[16]  O. Ptitsyn.  Thermodynamic parameters of helix-coil transitions in polypeptide chains , 1972, Pure and applied chemistry. Chimie pure et appliquee.

[17]  B. Matthews,et al.  Toward a simplification of the protein folding problem: a stabilizing polyalanine alpha-helix engineered in T4 lysozyme. , 1991, Biochemistry.

[18]  N R Kallenbach,et al.  Side chain contributions to the stability of alpha-helical structure in peptides. , 1990, Science.

[19]  H. Scheraga,et al.  Helix‐coil stability constants for the naturally occurring amino acids in water. XXIV. Half‐cystine parameters from random poly(hydroxybutylglutamine‐CO‐S‐methylthio‐L‐cysteine) , 1990 .

[20]  W. J. Becktel,et al.  Protein stability curves , 1987, Biopolymers.

[21]  F M Richards,et al.  Areas, volumes, packing and protein structure. , 1977, Annual review of biophysics and bioengineering.

[22]  R. Williams,et al.  Secondary structure predictions and medium range interactions. , 1987, Biochimica et biophysica acta.

[23]  Differential helix propensity of small apolar side chains studied by molecular dynamics simulations. , 1992, Biochemistry.

[24]  Harold A. Scheraga,et al.  The Influence of Amino Acid Side Chains on the Free Energy of Helix-Coil Transitions1 , 1966 .

[25]  B. Matthews,et al.  Enhanced protein thermostability from site-directed mutations that decrease the entropy of unfolding. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Hamlin,et al.  [27] Multiwire area X-ray diffractometers , 1985 .

[27]  W. DeGrado,et al.  A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids. , 1990, Science.

[28]  G. Rose,et al.  Side-chain entropy opposes alpha-helix formation but rationalizes experimentally determined helix-forming propensities. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Y. Chou,et al.  Empirical predictions of protein conformation. , 1978, Annual review of biochemistry.

[30]  Michael G. Rossmann,et al.  Processing oscillation diffraction data for very large unit cells with an automatic convolution technique and profile fitting , 1979 .

[31]  C. Chothia,et al.  Hydrophobic bonding and accessible surface area in proteins , 1974, Nature.

[32]  Thomas A. Kunkel,et al.  Rapid and efficient site-specific mutagenesis without phenotypic selection. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. Y. Chou,et al.  Conformational studies on copolymers of hydroxypropyl-L-glutamine and L-leucine. Circular dichroism studies. , 1972, Biochemistry.

[34]  B. Matthews,et al.  Second-site revertants of an inactive T4 lysozyme mutant restore activity by restructuring the active site cleft. , 1991, Biochemistry.