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| [[Image:1lya.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1lya| PDB=1lya | SCENE= }} | | {{STRUCTURE_1lya| PDB=1lya | SCENE= }} |
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| '''CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN'''
| | ===CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_8393577}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 8393577 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_8393577}} |
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| ==About this Structure== | | ==About this Structure== |
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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 00:25:07 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 22:48:45 2008'' |
