1lyb

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spinqualitylabelsall models PDB ID 1lyb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.5Å
Ligands:
Activity:	Cathepsin D, with EC number 3.4.23.5
Coordinates:	save as pdb, mmCIF, xml

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

1LYB is a Single protein structure of sequence from Homo sapiens. The following page contains interesting information on the relation of 1LYB with [Pepsin]. 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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