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| [[Image:1lyb.jpg|left|200px]] | | [[Image:1lyb.png|left|200px]] |
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| ==Overview==
| | {{ABSTRACT_8393577}} |
| Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play important roles in protein catabolism, antigen processing, degenerative diseases, and breast cancer progression. Determination of the crystal structures of cathepsin D and a complex with pepstatin at 2.5 A resolution provides insights into inhibitor binding and lysosomal targeting for this two-chain, N-glycosylated aspartic protease. Comparison with the structures of a complex of pepstatin bound to rhizopuspepsin and with a human renin-inhibitor complex revealed differences in subsite structures and inhibitor-enzyme interactions that are consistent with affinity differences and structure-activity relationships and suggest strategies for fine-tuning the specificity of cathepsin D inhibitors. Mutagenesis studies have identified a phosphotransferase recognition region that is required for oligosaccharide phosphorylation but is 32 A distant from the N-domain glycosylation site at Asn-70. Electron density for the crystal structure of cathepsin D indicated the presence of an N-linked oligosaccharide that extends from Asn-70 toward Lys-203, which is a key component of the phosphotransferase recognition region, and thus provides a structural explanation for how the phosphotransferase can recognize apparently distant sites on the protein surface.
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| ==About this Structure== | | ==About this Structure== |
| 1LYB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1LYB with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb12_1.html Pepsin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LYB OCA]. | | 1LYB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1LYB with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb12_1.html Pepsin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LYB OCA]. |
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| ==Reference==
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| Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design., Baldwin ET, Bhat TN, Gulnik S, Hosur MV, Sowder RC 2nd, Cachau RE, Collins J, Silva AM, Erickson JW, Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6796-800. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8393577 8393577]
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| [[Category: Cathepsin D]] | | [[Category: Cathepsin D]] |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
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| [[Category: Gulnik, S.]] | | [[Category: Gulnik, S.]] |
| [[Category: Lysosomal aspartic protease]] | | [[Category: Lysosomal aspartic protease]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:25:10 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:41:47 2008'' |
