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1lya
From Proteopedia
| 1lya, resolution 2.50Å () | |||||||||
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| Sites: | , , , , , , , , and | ||||||||
| Ligands: | , , | ||||||||
| Activity: | Cathepsin D, with EC number 3.4.23.5 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN
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.
About this Structure
1lya is a 4 chain structure of Cathepsin with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See Also
Reference
- Baldwin ET, Bhat TN, Gulnik S, Hosur MV, Sowder RC 2nd, Cachau RE, Collins J, Silva AM, Erickson JW. Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6796-800. PMID:8393577
