Cathepsin D Crystal Structures and Lysosomal Sorting

The D is not for dull! In this chapter we discuss the features of cathepsin D which are interesting because of their relevance to studies on lysosomal targeting. We will not describe the active site cleft, the centre of attention for aspartic proteinases with greater specificity or with more obvious medical significance. Mechanisms of protein targeting are of fundamental interest, and increasingly implicated in medicine. Unlike the aspartic proteases with previously known structures, cathepsin D is intracellular, and we solved crystal structures for human spleen cathepsin D and pepstatin inhibited bovine liver cathepsin D partly to learn more about what special features of this molecule cause it to be targeted to lysosomes1–3. There is one other solved structure of a lysosomal enzyme; the cysteine proteinase cathepsin B4. We are currently comparing its surface with that of cathepsin D to search for expected common features, as discussed in the following paragraphs.