Conformational studies on β‐bend containing a cis peptide unit

Abstract

Conformational studies have been carried out on the X-cis-Pro tripeptide system (a system of three linked peptide units, in the trans-cis-trans configuration) using energy minimization techniques. For X, residues Gly, L-Ala, D-Ala and L-Pro have been used. The energy minima have been classified into different groups based upon the conformational similarity. There are 15, 20, 18 and 6 minima that are possible for the four cases respectively arid these fall into 11 different groups. A study of these minima shows that, (i) some minima contain hydrogen bondseither 4-1 or 1-2 type, (ii) the low energy minima qualify themselves as bend conformations, (iii) cis' and trans' conformations are possible for the prolyl residue as also the 0 -e n d o and 0 -e x o puckerings, and (iv) for Pro-cis-Pro, cis' at the first prolyl residue is ruled out, due to the high energy. The available crystal structure data on proteins and peptides, containing cis-Pro segment have been examined with a view to find the minima that occur in solid state. The data from protein show that they fall under two groups. The conformation at X in X-cis-Pro is near extended when it is a non-glycyl residue. In both peptides and proteins there exists a preference for trans' conformation at prolyl residue over cis' when X is a non-glycyl residue. The minima obtained can be useful in modelling studies.

Turns revisited: A uniform and comprehensive classification of normal, open, and reverse turn families minimizing unassigned random chain portions

“…The putative occurrence of a reverse hydrogen bonding between NH i and CO i+x was first described by Toniolo4 and later supported for δ‐turns by a theoretical analysis performed by Nagarajaram et al 22. The present study provides the first general analysis of protein turn structures exhibiting a reverse hydrogen bond that reveals some interesting results.…”

“…He designated two residue “reverse” hydrogen bonded turns as δ‐turns and three residue “reverse” hydrogen‐bonded turns as ϵ‐turns. The existence of δ‐turns was later supported by theoretical conformational studies on three linked peptide units containing a cis‐Pro by Nagarajaram et al 22. To the best of our knowledge, δ‐turns were never described in proteins and ϵ‐turns have not been detected in proteins or peptides or during theoretical conformational analysis.…”

Peptide δ‐Turn: Literature Survey and Recent Progress

“…For the simplest (terminally protected) sequence ‐Gly‐ L ‐Pro‐, the most favorable backbone torsion angles according to ECEEP calculations were found to be ϕ 2 =173°, ψ 2 =85°, ϕ 3 =−75°, ψ 3 =167°28 (this dipeptide was selected for this study because Gly is the least sterically hindered among coded amino acids, and the Xxx‐Pro tertiary amide function is known to accommodate in the cis ‐conformation relatively often as compared to secondary amides) 1. 19, 21, 26, 32–37 Moreover, a stabilization of this turn structure was obtained when the amide torsion angle, ω , was allowed to fluctuate in the range ±10–15°. Interestingly, X‐ray diffraction investigations on medium‐sized lactams revealed that the eight‐membered ring compound of this class (enantholactam) is too small to accommodate a trans ‐amide conformation ( ω =180°) 38.…”

“…Interestingly, in a previous study in the crystal state by the same group,60 it was shown that the sequentially related cyclopentapeptide cyclo [ L ‐Ala‐ L ‐Pro‐Gly‐ D ‐Phe‐ L ‐Pro], although possessing a conformation at the ‐ L ‐Ala‐ L ‐Pro‐ dipeptide unit close to that of ‐Gly‐ L ‐Pro‐,59 appears not to form the intramolecularly H‐bonded δ‐turn. The authors attributed the absence (or the extremely weak character)32 of the H bond to the steric requirements of the L ‐residue at the left corner position of the putative C 8 conformer. In particular, the ϕ , ψ torsion angles of the Ala residue are found in the region of the left‐handed helix of the Ramachandran map, known to be unfavorable for an L ‐configured residue…”

Analysis of residue conformations in peptides in Cambridge structural database and protein‐peptide structural complexes

“…Initially, residues with ϕ > 0° and non‐ trans peptide bond were excluded. There are 17 PDB instances with 22 observations of cis peptide residues, and Gly, Ile, and Ala are the most frequent residues . In total, 67 PDBs with 114 residues have ϕ > 0°.…”