Peptide‐plane flipping in proteins

Abstract

A peptide-plane flip is a large-scale rotation of the peptide plane that takes the , angles at residues i and i + 1 to different structural regions in the Ramachandran plot with a comparatively small effect on the relative orientation of their side chains. This phenomenon, which is expected to play an important role during the early stages of protein folding, has been investigated using 76 proteins for which two highresolution X-ray conformations are available. Peptide-plane flips are identified by looking for those cases where changes in | i | + | i + 1 | are large (>200°), but changes in | i + i + 1 | are comparatively small (<50°). Of a total of 23 cases, the most common peptide-plane flip was identified to be the type I to type II ␤-turn interconversion. Although individually rarer, there are many other types of flips that are collectively more common. Given the four main accessible regions ␣ R , ␣ L , ␤ and , identified from the , distribution corresponding to non-hydrogen-bonded peptide planes, 32 main types of peptide-plane flip are identified. Only 8 of these are "passive," in that they require only relatively minor adjustments in the orientation of adjacent peptide planes. Of these, only the type I to type II ␤-turn interconversion, denoted, Keywords: Backbone dihedrals; Ramachandran plot; left-handed ␣-helix; protein folding; structural interconversion Some time ago Diamond (1965) pointed out that the path traced out by C ␣ atoms depends largely on i + i + 1 , whereas the orientations of the intervening peptide planes depend mainly on i − i + 1 . This can be appreciated by noting that for peptides in the trans conformation, the C ␣ -C bond vector, the -dihedral axis of residue i, is almost parallel to the N-C ␣ bond vector of residue i + 1, the -dihedral axis of residue i + 1. This implies that, all other angles remaining unchanged, ⌬ i + ⌬ i + 1 gives the approximate rotation of all groups on the C-terminal side of the peptide plane (the "tail"), including the side chain of residue i + 1, relative to all groups on the N-terminal side of the plane (the "head"), including the side chain of residue i. If the side chains of adjacent residues are unable to undergo a relative rotation then the intervening peptide plane may still undergo a large rotation, provided ⌬ i + ⌬ i + 1 is small. In proteins, large isolated backbone dihedral angle rotations are expected to occur only at the termini. Elsewhere, compensating changes will occur. Peptide-plane rotations represent the most local form of compensation in dihedral angle changes whereby changes in i are accompanied by compensating changes in i + 1 . Although the two dihedral axes are almost parallel, they are not colinear and large counter-rotations do result in small relative translations of the side chains.In this paper, a peptide-plane flip is defined to be a largescale rotation of the peptide plane that takes the , angles at residue i and i + 1 to different structural (stable) regions

How Different are Structurally Flexible and Rigid Binding Sites? Sequence and Structural Features Discriminating Proteins that Do and Do not Undergo Conformational Change upon Ligand Binding

“…Most changes that appear large (based on the length of the line) are not really large dihedral angle changes considering the fact that dihedral angles vary from −180°to +180°. Further, it is known that peptide bond flip that results in α-helical to extended conformational (or vice versa) transitions do occur when structural variants are compared; 58,59 and indeed varying ligand sizes will have some effect on the protein conformations.…”

Parameterization and Analysis of Peptide-Based Catalysts for the Atroposelective Bromination of 3-Arylquinazolin-4(3H)-ones

“…6 For instance, type I′ and II′ β-turns, differing mainly by the orientation of the loop amide region (blue boxes, Figure 1b), 7 have been observed in the solid and solution states for several variations of 3 . 8 Ultimately, methods to simultaneously interrogate the flexibility and dynamics of these catalysts will facilitate an understanding of the enantioselectivity imparted in a given reaction and provide additional opportunities to predict new peptide catalyst performance.…”

Structural studies of β-turn-containing peptide catalysts for atroposelective quinazolinone bromination

“…Dimethyl amides are generally presumed to be stronger H-bond acceptors than methyl esters. 14 It seems plausible that a weakened N H Dmaa to O Leu (hairpin) H-bond could produce a significant geometric change, especially when paired with backbone conformational driving forces, such as the more helical tendencies of Acpc. 13 …”