Prolylproline unit in model peptides and in fragments from databases

Abstract

The prolylproline sequence unit is found in several naturally occurring linear and cyclic peptides with immunosuppressive and toxic activity. Furthermore, Pro-Pro units are abundant in collagen, in ligand motifs binding to SH3 or WW domains, as well as in vital enzymes such as DNA glycosylase and thrombin. In all these sequence units a special role is dedicated to conformation in order to successfully fulfill the appropriate biological function. Therefore, a detailed analysis of the basic conformational properties of Pro-Pro is expected to reveal the versatile structural role of this sequence. PCM (polarizable continuum model) calculations on the basis of ab initio and density functional theory investigations using the model peptide HCO-L-Pro-L-Pro-NH2 are presented. Cis-trans isomerism, backbone conformation and ring puckering are studied. A systematic comparison is made to experimental data gained on L-prolyl-L-proline sequence units retrieved from the Protein Data Bank as well as from the Cambridge Structural Database. PCM data are in good agreement with high-resolution X-ray crystallography. Population data derived from energy calculations and those gained directly from statistics predict that 87% of the Pro-Pro sequence units adopt elongated structures, while 13% form beta-turns. Both approaches prefer the same 6 out of the 36 ideally possible backbone folds. Polyproline II unit (t epsilonL t epsilonL), other elongated structures (c epsilonL t epsilonL, t epsilonL t alphaL and t epsilonL t gammaL), type VIa (t epsilonL c alphaL) and type I or III beta-turns (t alphaL t alphaL) altogether describe 96% of the prolylproline sequences. In disordered proteins or domains, Pro-Pro sequence units may sample the various conformers and contribute to the segmental motions.

β‐turn tendency in N‐methylated peptides with dehydrophenylalanine residue: DFT study

“…Because of the limited accuracy of both methods the differences between conformers energies less than 1 kcal/mol mean comparable stability of the structures and are not the evidence of the favoring of one structure over another. Relatives energies were used to obtain information about the estimated abundances of given backbone conformers 39…”

The nucleotide addition cycle of RNA polymerase is controlled by two molecular hinges in the Bridge Helix domain

“…The activity of the Q823-P/S824-P double mutant proves explicitly that the presence of two proline residues in this particular location of the Bridge Helix is not only compatible with catalytic function, but also compatible with superactivity. Prolyl-proline preferentially adopt an elongated polyproline II structure (87%), or less frequently (13%) a β-turn (Additional file 4A; [43,44]). Either of the structures would cause a substantial local increase in the flexibility of BH-H C .…”

The influence of solvent on conformational properties of peptides with Aib residue—a DFT study

“…For each conformer, we performed vibrational analysis to check the absence of imaginary freuqencies. The abundances p of individual conformers were estimated on the basis of the relative energies [ 55 ]. The regions of the Ramachandran map are employed as conformational descriptors for backbone orientations of peptides and are labeled differently by different research groups.…”