Distance-based global analysis of consistentcis-bonds in protein backbones

Abstract

AbstractBiological polypeptides are known to containcis-linkage in their main chain as a minor but important feature. Such anomalous connection of amino acids has different structural and functional effects on proteins. Experimental evidence ofcis-bonds in proteins is mainly obtained using X-ray crystallography and other methods in the field of structural biology. To date, extensive analyses have been carried out on the experimentally foundcis-bonds using the Protein Data Bank entry bases and/or residue bases; however, their consistency in each protein has not been examined on a global scale. Data accumulation and advances in methodology enable the use of new approaches from a proteomic point of view. Here, we sought to describe a simple procedure for the detection and confirmation ofcis-bonds from a set of experimental coordinates for a protein to discriminate this type of bond from isomerizable and/or misassigned bonds. The resulting set of consistentcisbonds provides unprecedented insights into the trend of “highciscontent” proteins and the upper limit of consistentcisbonds per polypeptide length. Recognizing such limit would not only be important for a practical check of upcoming structures, but also for the design of novel protein folds beyond the evolutionally-acquired repertoire.