D‐amino acid residues in peptides and proteins

Abstract

We have investigated the D-amino acid residues present in Protein Data Bank (PDB) entries, categorizing them into "real" D-residues and artifacts. In polypeptide chains of more than 20 residues, only a single instance of a "real" D-residue, other than those deliberately designed or engineered, was found. This example was the result of a slow chemical epimerization process. Another 12 designed D-residues were found in these longer polypeptide chains. Smaller peptides of 20 or fewer residues contained 479 "real" D-residues, the majority in various gramicidin, actinomycin, or cyclosporin structures. We found 148 PDB entries with "real" D-residues and a further 186, in which all apparent D-residues are artifacts. Investigating the (phi, psi) preferences of the "real" D-residues, we found that the region around (-60 degrees, -45 degrees ) was almost completely unoccupied, even though it is not formally disallowed. We link the low propensity to occupy this region with the alpha-helix destabilizing properties of D-residues.

Crystal Structure and Structural Mechanism of a Novel Anti-Human Immunodeficiency Virus andd-Amino Acid-Containing Chemokine

“…occupied the "inverted ␣-helix (L)" region around Ϫ60°and Ϫ45°, which is consistent with the alpha helix-destabilizing properties of D-amino acids and the propensity of D-amino acids to promote ␤-turn formation (27,45). All of the amino acid residues, including both D and L forms, adopt the trans conformation for the amide bond.…”

Reconstruction of the Conserved β-Bulge in Mammalian Defensins Using d-Amino Acids

“…Mitchell and Smith (19) categorize the D-amino acid residues present in Protein Data Bank entries and find that the torsion angles preferred by the vast majority of D-residues are loosely centered around ϭ ϩ120°and ϭ Ϫ135°, with a small portion around the ␣ L region (ϩ60°, ϩ45°). It is therefore reasonable to assume that substitutions of D-amino acids for Gly 17 in defensins will introduce little perturbation on the protein structure because of local conformational compatibility.…”

“…2) (18). These torsion angles are rarely observed for L-amino acid residues but are energetically preferable for D-enantiomers (19). Thus, we hypothesized that the glycyl residue is conserved in mammalian ␣-defensins because of the stringent structural requirement for ␤-bulges that cannot be met by any L-amino acids with restricted backbone conformational space.…”

Invariant Gly Residue Is Important for α-Defensin Folding, Dimerization, and Function

“…It was shown previously that the invariant Gly 17 residue in ␣-defensins typically adopts the backbone dihedral angles (, ) centered at ϭ 170°and ϭ Ϫ150°in the Ramachandran diagram, a region disallowed for L-amino acids but permissible for D-enantiomers (18,43). A torsion angle analysis of L-Ala 17 in the four structurally independent monomers indicates that it adopts the (, ) angles centered at ϭ Ϫ163°Ϯ 3.4, ϭ Ϫ163°Ϯ 5.1 in an allowed but much less common ␤-sheet region for L-amino acid residues (Fig.…”