1lya

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spinqualitylabelsall models 1lya, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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

1LYA is a Single protein structure of sequence from Homo sapiens with NAG as ligand. 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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