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1lyw

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Revision as of 06:46, 10 September 2015

CATHEPSIN D AT PH 7.5

Structural highlights

1lyw is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Cathepsin D, with EC number 3.4.23.5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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.

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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1lyw"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lyw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1lyw RCSB], [http://www.ebi.ac.uk/pdbsum/1lyw PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lyw OCA], [http://pdbe.org/1lyw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lyw RCSB], [http://www.ebi.ac.uk/pdbsum/1lyw PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1lyw" style="background-color:#fffaf0;"></div>
 ==See Also==

1lyw

From Proteopedia

Revision as of 06:46, 10 September 2015

CATHEPSIN D AT PH 7.5

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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