1lyb
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Pepsin]] | [[Category: Pepsin]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baldwin, E | + | [[Category: Baldwin, E T.]] |
| - | [[Category: Bhat, T | + | [[Category: Bhat, T N.]] |
| - | [[Category: Erickson, J | + | [[Category: Erickson, J W.]] |
[[Category: Gulnik, S.]] | [[Category: Gulnik, S.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: lysosomal aspartic protease]] | [[Category: lysosomal aspartic protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:49:33 2008'' |
Revision as of 11:49, 21 February 2008
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CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Ceroid lipofuscinosis, neuronal, 10 OMIM:[116840]
About this Structure
1LYB is a Single protein structure of sequence from Homo sapiens with as ligand. The following page contains interesting information on the relation of 1LYB with [Pepsin]. Active as Cathepsin D, with EC number 3.4.23.5 Full crystallographic information is available from OCA.
Reference
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:8393577
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