|
|
| Line 4: |
Line 4: |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1lyw]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LYW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LYW FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1lyw]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LYW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LYW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cathepsin_D Cathepsin D], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.5 3.4.23.5] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lyw OCA], [https://pdbe.org/1lyw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lyw RCSB], [https://www.ebi.ac.uk/pdbsum/1lyw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lyw ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lyw OCA], [https://pdbe.org/1lyw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lyw RCSB], [https://www.ebi.ac.uk/pdbsum/1lyw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lyw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:[https://omim.org/entry/610127 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.<ref>PMID:16670177</ref> <ref>PMID:16685649</ref> <ref>PMID:21990111</ref>
| + | [https://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN] Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:[https://omim.org/entry/610127 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.<ref>PMID:16670177</ref> <ref>PMID:16685649</ref> <ref>PMID:21990111</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
| + | [https://www.uniprot.org/uniprot/CATD_HUMAN 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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 38: |
Line 38: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cathepsin D]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Erickson, J W]] | + | [[Category: Erickson JW]] |
| - | [[Category: Gulnik, S V]] | + | [[Category: Gulnik SV]] |
| - | [[Category: Lee, A Y]] | + | [[Category: Lee AY]] |
| - | [[Category: Aspartic protease]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
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.[1] [2] [3]
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
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.
Conformational switching in an aspartic proteinase.,Lee AY, Gulnik SV, Erickson JW Nat Struct Biol. 1998 Oct;5(10):866-71. PMID:9783744[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Siintola E, Partanen S, Stromme P, Haapanen A, Haltia M, Maehlen J, Lehesjoki AE, Tyynela J. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain. 2006 Jun;129(Pt 6):1438-45. Epub 2006 May 2. PMID:16670177 doi:10.1093/brain/awl107
- ↑ Steinfeld R, Reinhardt K, Schreiber K, Hillebrand M, Kraetzner R, Bruck W, Saftig P, Gartner J. Cathepsin D deficiency is associated with a human neurodegenerative disorder. Am J Hum Genet. 2006 Jun;78(6):988-98. Epub 2006 Mar 29. PMID:16685649 doi:10.1086/504159
- ↑ Kousi M, Lehesjoki AE, Mole SE. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. PMID:21990111 doi:10.1002/humu.21624
- ↑ Lee AY, Gulnik SV, Erickson JW. Conformational switching in an aspartic proteinase. Nat Struct Biol. 1998 Oct;5(10):866-71. PMID:9783744 doi:http://dx.doi.org/10.1038/2306
|
