1lyb
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CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Ceroid lipofuscinosis, neuronal, 10 OMIM:[116840]
About this StructureAbout this Structure
1LYB is a Single protein structure of sequence from Homo sapiens with NAG 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.
ReferenceReference
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 Mon Nov 12 18:05:11 2007