Non-proline cis peptide bonds in proteins

In a non-redundant set of 571 proteins from the Brookhaven Protein Data Bas e, a total of 43 non-proline cis peptide bonds were identified. Average geo metrical parameters of the well-defined cis peptide bonds in proteins deter mined at high resolution show that some parameters, most notably the bond a ngle at the amide bond nitrogen, deviate significantly from the correspondi ng one in the trans conformation. Since the same feature was observed in ci s amide bonds in small molecule structures found in the Cambridge Structura l Data Base, a new set of parameters for the refinement of protein structur es containing non-Pro cis peptide bonds is proposed. A striking preference was observed for main-chain dihedral angles of the re sidues involved in cis peptide bonds. All residues N-terminal and most resi dues C-terminal to a non-Pro cis peptide bond (except Gly) are located in t he beta-region of a phi/psi plot. Also, all of the few C-terminal residues (except Gly) located in the alpha-region of the phi/psi plot constitute the start of an alpha-helix in the respective structure. In the majority of cases, an intimate side-chain/side-chain interaction was observed between the flanking residues, often involving aromatic side-chai ns. Interestingly, most of the cases found occur in functionally important regions such as close to the active site of proteins. It is intriguing that many of the proteins containing non-proline cis peptide bonds are carbohyd rate-binding or processing proteins. The occurrence of these unusual peptide bonds is significantly more frequen t in structures determined at high resolution than in structures determined at medium and low resolution, suggesting that these bonds may be more abun dant than previously thought. On the basis of our experience with the struc ture determination of coagulation factor XIII, we developed an algorithm fo r the identification of possibly overlooked cis peptide bonds that exploits the deviations of geometrical parameters from ideality. A few likely candi dates based on our algorithm have been identified and are discussed. (C) 19 99 Academic Press.