1lyb | pdb_00001lyb

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

spinqualitylabelsall models 1lyb, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1lyb is a 6 chain structure with sequence from Homo sapiens and Streptomyces argenteolus subsp. toyonakensis. The December 2000 RCSB PDB Molecule of the Month feature on Pepsin by David S. Goodsell is 10.2210/rcsb_pdb/mom_2000_12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: BMA, IVA, MAN, NAG, STA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CATD_HUMAN Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:610127; also known as neuronal ceroid lipofuscinosis due to cathepsin D deficiency. A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. Function CATD_HUMAN Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cathepsin 3D structures

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