Two crystal structures for cathepsin D: the lysosomal targeting signal and active site.

Research Article1 April 1993free access Two crystal structures for cathepsin D: the lysosomal targeting signal and active site. P. Metcalf P. Metcalf European Molecular Biology Laboratory, Heidelberg, Germany. Search for more papers by this author M. Fusek M. Fusek European Molecular Biology Laboratory, Heidelberg, Germany. Search for more papers by this author P. Metcalf P. Metcalf European Molecular Biology Laboratory, Heidelberg, Germany. Search for more papers by this author M. Fusek M. Fusek European Molecular Biology Laboratory, Heidelberg, Germany. Search for more papers by this author Author Information P. Metcalf1 and M. Fusek1 1European Molecular Biology Laboratory, Heidelberg, Germany. The EMBO Journal (1993)12:1293-1302https://doi.org/10.1002/j.1460-2075.1993.tb05774.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Two crystal structures are described for the lysosomal aspartic protease cathepsin D (EC 3.4.23.5). The molecular replacement method was used with X-ray diffraction data to 3 A resolution to produce structures for human spleen cathepsin D and for bovine liver cathepsin D complexed with the 6-peptide inhibitor pepstatin A. The lysosomal targeting region of cathepsin D defined by previous expression studies [Barnaski et al. (1990) Cell, 63, 281–219] is located in well defined electron density on the surface of the molecules. This region includes the putative binding site of the cis-Golgi phosphotransferase which is responsible for the initial sorting step for soluble proteins destined for lysosomes by phosphorylating the carbohydrates on these molecules. Carbohydrate density is visible at both expected positions on the cathepsin D molecules and, at the best defined position, four sugar residues extend towards the lysosomal targeting region. The active site of the protease and the active site cleft substrate binding subsites are described using the pepstatin inhibited structure. The model geometry for human cathepsin D has rms deviations from ideal of bonds and angles of 0.013 A and 3.2 degrees respectively. For bovine cathepsin D the corresponding figures are 0.014 A and 3.3 degrees. The crystallographic residuals (R factors) are 16.1% and 15.8% for the human and inhibited bovine cathepsin D models respectively. The free R factors, calculated with 10% of the data reserved for testing the models and not used for refinement, are 25.1% and 24.1% respectively. Previous ArticleNext Article Volume 12Issue 41 April 1993In this issue RelatedDetailsLoading ...