ArticleProtein science : a publication of the Protein Society1993
Exploration of subsite binding specificity of human cathepsin D through kinetics and rule-based molecular modeling.
Article in Protein science : a publication of the Protein Society, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 100 citations in OpenAlex.
- A fluorogenic, peptide-based probe for the detection of Cathepsin D in macrophages.Communications chemistry · 2023Article
- Enzymatic Characterization of Recombinant Food Vacuole Plasmepsin 4 from the Rodent Malaria Parasite Plasmodium berghei.PloS one · 2015Article
- Molecular imaging of Cathepsin E-positive tumors in mice using a novel protease-activatable fluorescent probe.Molecular bioSystems · 2011Article
- Selective detection of Cathepsin E proteolytic activity.Biochimica et biophysica acta · 2010Article
- Protease cleavage sites in HIV-1 gp120 recognized by antigen processing enzymes are conserved and located at receptor binding sites.Journal of virology · 2010Article
- Recombinant plasmepsin 1 from the human malaria parasite plasmodium falciparum: enzymatic characterization, active site inhibitor design, and structural analysis.Biochemistry · 2009Article
- Synthesis and in vitro characterization of novel dextran-methylprednisolone conjugates with peptide linkers: effects of linker length on hydrolytic and enzymatic release of methylprednisolone and its peptidyl intermediates.Journal of pharmaceutical sciences · 2008Article
- Modification of the substrate specificity of porcine pepsin for the enzymatic production of bovine hide gelatin.Protein science : a publication of the Protein Society · 2000Article
- Alpha1-antichymotrypsin and kallistatin hydrolysis by human cathepsin D.Journal of protein chemistry · 2000Article
- Active site specificity of plasmepsin II.Protein science : a publication of the Protein Society · 1999Article
- Prime region subsite specificity characterization of human cathepsin D: the dominant role of position 128.Protein science : a publication of the Protein Society · 1998Article
- Structure-based subsite specificity mapping of human cathepsin D using statine-based inhibitors.Protein science : a publication of the Protein Society · 1997Article
- Crystal structure of human pepsin and its complex with pepstatin.Protein science : a publication of the Protein Society · 1995Article
- Engineering the substrate specificity of rhizopuspepsin: the role of Asp 77 of fungal aspartic proteinases in facilitating the cleavage of oligopeptide substrates with lysine in P1.Protein science : a publication of the Protein Society · 1995Article
- Studies on the specificity of acetylaminoacyl-peptide hydrolase.Protein science : a publication of the Protein Society · 1994Article
- Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.Proceedings of the National Academy of Sciences of the United States of America · 1993Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The family of aspartic proteinases includes several human enzymes that may play roles in both physiological and pathophysiological processes. The human lysosomal aspartic proteinase cathepsin D is thought to function in the normal degradation of intracellular and endocytosed proteins but has also emerged as a prognostic indicator of breast tumor invasiveness. Presented here are results from a continuing effort to elucidate the factors that contribute to specificity of ligand binding at individual subsites within the cathepsin D active site. The synthetic peptide Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu has proven to be an excellent chromogenic substrate for cathepsin D yielding a value of kcat/Km = 0.92 x 10(-6) s-1 M-1 for enzyme isolated from human placenta. In contrast, the peptide Lys-Pro-Ala-Lys-Phe*Nph-Arg-Leu and all derivatives with Ala-Lys in the P3-P2 positions are either not cleaved at all or cleaved with extremely poor efficiency. To explore the binding requirements of the S3 and S2 subsites of cathepsin D, a series of synthetic peptides was prepared with systematic replacements at the P2 position fixing either Ile or Ala in P3. Kinetic parameters were determined using both human placenta cathepsin D and recombinant human fibroblast cathepsin D expressed in Escherichia coli. A rule-based structural model of human cathepsin D, constructed on the basis of known three-dimensional structures of other aspartic proteinases, was utilized in an effort to rationalize the observed substrate selectivity.
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