1lya: Difference between revisions
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New page: left|200px<br /> <applet load="1lya" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lya, resolution 2.5Å" /> '''CRYSTAL STRUCTURES O... |
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[[Image:1lya.gif|left|200px]]<br /> | [[Image:1lya.gif|left|200px]]<br /><applet load="1lya" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1lya" size=" | |||
caption="1lya, resolution 2.5Å" /> | caption="1lya, resolution 2.5Å" /> | ||
'''CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN'''<br /> | '''CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN'''<br /> | ||
==Overview== | ==Overview== | ||
Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1LYA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | 1LYA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LYA OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Baldwin, E | [[Category: Baldwin, E T.]] | ||
[[Category: Bhat, T | [[Category: Bhat, T N.]] | ||
[[Category: Erickson, J | [[Category: Erickson, J W.]] | ||
[[Category: Gulnik, S.]] | [[Category: Gulnik, S.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: lysosomal aspartic protease]] | [[Category: lysosomal aspartic protease]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:49:35 2008'' | ||
