Intrahelical hydrogen bonding of serine, threonine and cysteine residues within alpha-helices and its relevance to membrane-bound proteins.

A survey of known protein structures reveals that approximately 70% of serine residues and at least 85% (potentially 100%) of threonine residues in helices make hydrogen bonds to carbonyl oxygen atoms in the preceding turn of the helix. The high frequency of intrahelical hydrogen bonding is of particular significance for intrinsic membrane-bound proteins that form transmembrane helices. Hydrogen bonding within a helix provides a way for serine, threonine and cysteine residues to satisfy their hydrogen-bonding potential permitting such residues to occur in helices buried within a hydrophobic milieu.

[1]  W. Bode,et al.  The refined crystal structure of bovine beta-trypsin at 1.8 A resolution. II. Crystallographic refinement, calcium binding site, benzamidine binding site and active site at pH 7.0. , 1975, Journal of molecular biology.

[2]  P. Argos,et al.  Will the seven‐helix bundle be a common structure for integral membrane proteins? , 1983 .

[3]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1977, Journal of molecular biology.

[4]  G. N. Ramachandran,et al.  Studies on the conformation of amino acids. XI. Analysis of the observed side group conformation in proteins. , 2009, International journal of protein research.

[5]  G. N. Ramachandran,et al.  Conformation of polypeptides and proteins. , 1968, Advances in protein chemistry.

[6]  L. Sieker,et al.  Adjustment of restraints in the refinement of methemerythrin and azidomethemerythrin at 2.0 Å resolution , 1983 .

[7]  M. Levitt,et al.  Conformation of amino acid side-chains in proteins. , 1978, Journal of molecular biology.

[8]  T. Bhat,et al.  An analysis of side-chain conformation in proteins. , 2009, International journal of peptide and protein research.

[9]  T. Steitz,et al.  The spontaneous insertion of proteins into and across membranes: The helical hairpin hypothesis , 1981, Cell.

[10]  S. D. Dover,et al.  Refinement of bond angles of an α-helix , 1967 .

[11]  M. James,et al.  Structure and refinement of penicillopepsin at 1.8 A resolution. , 1983, Journal of molecular biology.

[12]  J. Kraut,et al.  Polypeptide halomethyl ketones bind to serine proteases as analogs of the tetrahedral intermediate. X-ray crystallographic comparison of lysine- and phenylalanine-polypeptide chloromethyl ketone-inhibited subtilisin. , 1976, The Journal of biological chemistry.

[13]  R. Huber,et al.  The Geometry of the Reactive Site and of the Peptide Groups in Trypsin, Trypsinogen and its Complexes with Inhibitors , 1983 .

[14]  R. Stroud,et al.  Structure of bovine trypsinogen at 1.9 A resolution. , 1977, Biochemistry.

[15]  R. Capaldi.  Structure of intrinsic membrane proteins , 1982 .

[16]  Gunnar von Heijne,et al.  On the Hydrophobic Nature of Signal Sequences , 1981 .

[17]  P. Argos,et al.  Structural prediction of membrane-bound proteins. , 2005, European journal of biochemistry.

[18]  R. Huber,et al.  Crystal structure analysis and refinement of two variants of trigonal trypsinogen , 1978, FEBS letters.

[19]  J. Sanders-Loehr,et al.  Structure of the binuclear iron complex in metazidohaemerythrin from Themiste dyscritum at 2.2. Å resolution , 1981, Nature.

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