β‐Bend conformation of CH3CO‐Pro‐Pro‐Gly‐Pro‐NHCH3: Implications for posttranslational proline hydroxylation in collagen

Conformational‐energy computations have been carried out for the N‐acetyl‐N′‐methylamides of the Pro‐Pro, Pro‐Gly, and Gly‐Pro dipeptides and of the Pro‐Pro‐Gly‐Pro tetrapeptide, serving as models for the conformational analysis of single‐stranded poly(Gly‐Pro‐Pro). The probability of β‐bend formation for the Pro‐Gly sequence is very high, viz., 0.72 for the terminally blocked Pro‐Gly dipeptide, and rises to 0.86 in the tetrapeptide. The β‐bend conformations of the Pro‐Gly sequence are of low energy in single‐chain poly(Gly‐Pro‐Pro) as well. The β‐bend structure had been postulated earlier to be a requirement for post‐translational proline hydroxylation during the biosynthesis of collagen. The present results lend strong support to this proposal by demonstrating that the β‐bend structure is energetically favorable and hence can be accommodated easily in single‐stranded poly(Gly‐Pro‐Pro).

[1]  H. Scheraga,et al.  Energy parameters in polypeptides. VII. Geometric parameters, partial atomic charges, nonbonded interactions, hydrogen bond interactions, and intrinsic torsional potentials for the naturally occurring amino acids , 1975 .

[2]  R. Rapaka,et al.  Hydroxylation of proline in polytripeptide models of collagen: stereochemistry of polytripeptide-prolyl hydroxylase interaction. , 1978, Biochemistry.

[3]  V. Renugopalakrishnan,et al.  THE TETRAPEPTIDE, HCO–L-Ala–L-Pro–Gly–Gly–OMe: CONFORMATIONS AND SOLVENT EFFECTS , 1981 .

[4]  H. Balaram,et al.  Multiple conformational states of a Pro-Pro peptide. Solid-state and solution conformations of Boc-Aib-Pro-Pro-NHMe , 1983 .

[5]  K. Kopple,et al.  Studies of peptide conformation. Evidence for beta structures in solutions of linear tetrapeptides containing proline. , 1975, Journal of the American Chemical Society.

[6]  K. Wüthrich,et al.  The X‐Pro peptide bond as an nmr probe for conformational studies of flexible linear peptides , 1976, Biopolymers.

[7]  S. Brahmachari,et al.  Beta-turns in nascent procollagen are sites of posttranslational enzymatic hydroxylation of proline. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Brahmachari,et al.  Polypeptide models of collagen. II. Solution properties of (Pro‐Gly‐Phe)n , 1978, Biopolymers.

[9]  H. Scheraga,et al.  Local interactions in bends of proteins. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Brahmachari,et al.  Proline‐containing β‐turns in peptides and proteins. II. Physicochemical studies on tripeptides with the Pro‐Gly sequence , 1982 .

[11]  R. Rapaka,et al.  Synthetic Polypeptide Models of Collagen: Synthesis and Applications , 1976 .

[12]  P. Y. Chou,et al.  β-turns in proteins☆ , 1977 .

[13]  E. Blout,et al.  Conformations of (X-L-Pro-Y)2 cyclic hexapeptides. Preferred beta-turn conformers and implications for beta turns in proteins. , 1981, Biochemistry.

[14]  K. Kivirikko,et al.  Posttranslational enzymes in the biosynthesis of collagen: intracellular enzymes. , 1982, Methods in enzymology.

[15]  H. Scheraga,et al.  Chain reversals in proteins. , 1973, Biochimica et biophysica acta.

[16]  G. Némethy.  Interactions between poly(Gly‐Pro‐Pro) triple helices: A model for molecular packing in collagen , 1983, Biopolymers.

[17]  R. Chopra,et al.  Conformational implications of enzymatic proline hydroxylation in collagen. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[18]  T. Bhat,et al.  .beta.-Turn conformation of N-acetyl-L-prolylglycyl-L-phenylalanine. Crystal structure and solution studies , 1981 .

[19]  H. Scheraga,et al.  Influence of local interactions on protein structure. I. Conformational energy studies of N‐acetyl‐N′‐methylamides of pro‐X and X‐pro dipeptides , 1977, Biopolymers.

[20]  Nuclear magnetic resonance and conformational energy calculations of repeat peptides of elastin. Conformational characterization of cyclopentadecapeptide cyclo-(L-Val-L-Pro-Gly-L-Val-Gly)3 , 1981 .

[21]  H. Scheraga,et al.  Computed conformational states of the 20 naturally occurring amino acid residues and of the prototype residue α-aminobutyric acid , 1983 .

[22]  H. Scheraga,et al.  Conformational analysis of the 20 naturally occurring amino acid residues using ECEPP. , 1977, Macromolecules.

[23]  H. Scheraga,et al.  Energy parameters in polypeptides. 9. Updating of geometrical parameters, nonbonded interactions, and hydrogen bond interactions for the naturally occurring amino acids , 1983 .

[24]  C. Venkatachalam.  Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units , 1968, Biopolymers.

[25]  S. Rackovsky,et al.  Characterization of multiple bends in proteins , 1980, Biopolymers.

[26]  H. Scheraga,et al.  Conformational studies of oligopeptides containing proline and glycine. , 1977, Macromolecules.

[27]  J. Uitto,et al.  Intracellular Steps in the Biosynthesis of Collagen , 1976 .

[28]  R. Bhatnagar.  INTERACTION BETWEEN PROLYL HYDROXYLASE AND ITS POLYPEPTIDE SUBSTRATE , 1981 .

[29]  I. C. O. B. Nomenclature.  IUPAC-IUB Commission on Biochemical Nomenclature. Abbreviations and symbols for the description of the conformation of polypeptide chains. Tentative rules (1969). , 1970, Biochemistry.

[30]  D. Urry,et al.  Nuclear Overhauser enhancement demonstration of the type II beta-turn in repeat peptides of tropoelastin. , 1976, Biochemical and biophysical research communications.

[31]  A. Verdini,et al.  13C nuclear magnetic resonance study of the triple helix ⇌ random-coil transition of (prolylprolyglycyl)10 , 1979 .