1lyb: Difference between revisions
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|PDB= 1lyb |SIZE=350|CAPTION= <scene name='initialview01'>1lyb</scene>, resolution 2.5Å | |PDB= 1lyb |SIZE=350|CAPTION= <scene name='initialview01'>1lyb</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> | |LIGAND= <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=IVA:ISOVALERIC+ACID'>IVA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=STA:STATINE'>STA</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Cathepsin_D Cathepsin D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.5 3.4.23.5] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_D Cathepsin D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.5 3.4.23.5] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lyb OCA], [http://www.ebi.ac.uk/pdbsum/1lyb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lyb RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Erickson, J W.]] | [[Category: Erickson, J W.]] | ||
[[Category: Gulnik, S.]] | [[Category: Gulnik, S.]] | ||
[[Category: lysosomal aspartic protease]] | [[Category: lysosomal aspartic protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:08:52 2008'' | ||
