1lyw
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The crystal structure of a catalytically inactive form of cathepsin D | + | The crystal structure of a catalytically inactive form of cathepsin D (CatDhi) has been obtained at pH 7.5. The N-terminal strand relocates by 30 A from its position in the interdomain beta-sheet and inserts into the active site cleft, effectively blocking substrate access. CatDhi has a five-stranded interdomain beta-sheet and resembles Intermediate 3, a hypothetical structure proposed to be transiently formed during proteolytic activation of the proenzyme precursor. Interconversion between active and inactive forms of CatD is reversible and may be regulated by an ionizable switch involving the carboxylate side chains of Glu 5, Glu 180, and Asp 187. Our findings provide a structural basis for the pH-dependent regulation of aspartic proteinase activity and suggest a novel mechanism for pH-dependent modulation of substrate specificity. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Erickson, J | + | [[Category: Erickson, J W.]] |
| - | [[Category: Gulnik, S | + | [[Category: Gulnik, S V.]] |
| - | [[Category: Lee, A | + | [[Category: Lee, A Y.]] |
[[Category: EPE]] | [[Category: EPE]] | ||
[[Category: aspartic protease]] | [[Category: aspartic protease]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:49:43 2008'' |
Revision as of 11:49, 21 February 2008
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CATHEPSIN D AT PH 7.5
Contents |
Overview
The crystal structure of a catalytically inactive form of cathepsin D (CatDhi) has been obtained at pH 7.5. The N-terminal strand relocates by 30 A from its position in the interdomain beta-sheet and inserts into the active site cleft, effectively blocking substrate access. CatDhi has a five-stranded interdomain beta-sheet and resembles Intermediate 3, a hypothetical structure proposed to be transiently formed during proteolytic activation of the proenzyme precursor. Interconversion between active and inactive forms of CatD is reversible and may be regulated by an ionizable switch involving the carboxylate side chains of Glu 5, Glu 180, and Asp 187. Our findings provide a structural basis for the pH-dependent regulation of aspartic proteinase activity and suggest a novel mechanism for pH-dependent modulation of substrate specificity.
Disease
Known diseases associated with this structure: Ceroid lipofuscinosis, neuronal, 10 OMIM:[116840]
About this Structure
1LYW is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Cathepsin D, with EC number 3.4.23.5 Full crystallographic information is available from OCA.
Reference
Conformational switching in an aspartic proteinase., Lee AY, Gulnik SV, Erickson JW, Nat Struct Biol. 1998 Oct;5(10):866-71. PMID:9783744
Page seeded by OCA on Thu Feb 21 13:49:43 2008
