From Protein Structure to Function with Bioinformatics.pdf

312 I.A. Cymerman et al.Fig. 12.6 Structure of interleukin 4 showing the portion encoded by exon 2. The experimentalstructure (PDB code 1ilt) is shown as coloured cartoon, with exon 2-encoded protein colouredmagenta. Disulphide bridges are shown as sticks, with the bridge contributed to by exon 2-encoded protein shown as ball-and-stick12.4.7 From Broad Function to Molecular DetailsProtein function can be considered on different complexity levels – ranging from theinvolvement into the cellular processes to the knowledge of the mode of action onthe molecular level. Lysosomal deoxyribonuclease II α (DNase IIα) was one of theearliest endonucleases identified (1947), with considerable biochemical characterizationreported already in the 1960s. This enzyme is indispensable for the organismdevelopment as it is responsible for DNA waste removal and auxiliary apoptoticDNA fragmentation in higher eukaryotes – the knockout of murine lysosomalDNase IIα turned out to be lethal. Despite the intensive research for over 50 yearsand unquestionable importance of DNase IIα no similarity to any other protein familycould be detected, hampering function studies on the molecular level for this protein.No Fold Recognition method reported any target-template alignment with a scoreabove the documented level of significance, but analysis of their results revealed thatseveral of them reported a similarity to the phospholipase D (PLD) fold in the region