This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1lya
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1lya.gif|left|200px]] | [[Image:1lya.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1lya", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1lya| PDB=1lya | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''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''' | ||
| Line 30: | Line 27: | ||
[[Category: Erickson, J W.]] | [[Category: Erickson, J W.]] | ||
[[Category: Gulnik, S.]] | [[Category: Gulnik, S.]] | ||
| - | [[Category: | + | [[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 | + | |
Revision as of 21:25, 2 May 2008
CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN
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.
About this Structure
1LYA is a Single protein structure of sequence from Homo sapiens. 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 Page seeded by OCA on Sat May 3 00:25:07 2008
