4od9: Difference between revisions
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==Structure of Cathepsin D with inhibitor N-(3,4-dimethoxybenzyl)-Nalpha-{N-[(3,4-dimethoxyphenyl)acetyl]carbamimidoyl}-D-phenylalaninamide== | ==Structure of Cathepsin D with inhibitor N-(3,4-dimethoxybenzyl)-Nalpha-{N-[(3,4-dimethoxyphenyl)acetyl]carbamimidoyl}-D-phenylalaninamide== | ||
<StructureSection load='4od9' size='340' side='right' caption='[[4od9]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4od9' size='340' side='right'caption='[[4od9]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4od9]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OD9 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4od9]] is a 4 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=4OD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OD9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2RZ:N-(3,4-DIMETHOXYBENZYL)-NALPHA-{N-[(3,4-DIMETHOXYPHENYL)ACETYL]CARBAMIMIDOYL}-D-PHENYLALANINAMIDE'>2RZ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2RZ:N-(3,4-DIMETHOXYBENZYL)-NALPHA-{N-[(3,4-DIMETHOXYPHENYL)ACETYL]CARBAMIMIDOYL}-D-PHENYLALANINAMIDE'>2RZ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4od9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4od9 OCA], [https://pdbe.org/4od9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4od9 RCSB], [https://www.ebi.ac.uk/pdbsum/4od9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4od9 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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> | ||
== 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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 20: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4od9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cathepsin 3D structures|Cathepsin 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Czodrowski | [[Category: Large Structures]] | ||
[[Category: Graedler | [[Category: Czodrowski P]] | ||
[[Category: Klein | [[Category: Graedler U]] | ||
[[Category: Leuthner | [[Category: Klein M]] | ||
[[Category: Maskos | [[Category: Leuthner B]] | ||
[[Category: Tsaklakidis | [[Category: Maskos K]] | ||
[[Category: Tsaklakidis C]] | |||
Latest revision as of 10:15, 27 November 2024
Structure of Cathepsin D with inhibitor N-(3,4-dimethoxybenzyl)-Nalpha-{N-[(3,4-dimethoxyphenyl)acetyl]carbamimidoyl}-D-phenylalaninamideStructure of Cathepsin D with inhibitor N-(3,4-dimethoxybenzyl)-Nalpha-{N-[(3,4-dimethoxyphenyl)acetyl]carbamimidoyl}-D-phenylalaninamide
Structural highlights
DiseaseCATD_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] FunctionCATD_HUMAN Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease. Publication Abstract from PubMedWe discovered a novel series of non-peptidic acylguanidine inhibitors of Cathepsin D as target for osteoarthritis. The initial HTS-hits were optimized by structure-based design using CatD X-ray structures resulting in single digit nanomolar potency in the biochemical CatD assay. However, the most potent analogues showed only micromolar activities in an ex vivo glycosaminoglycan (GAG) release assay in bovine cartilage together with low cellular permeability and suboptimal microsomal stability. This new scaffold can serve as a starting point for further optimization towards in vivo efficacy. Structure-based optimization of non-peptidic Cathepsin D inhibitors.,Gradler U, Czodrowski P, Tsaklakidis C, Klein M, Werkmann D, Lindemann S, Maskos K, Leuthner B Bioorg Med Chem Lett. 2014 Jul 25. pii: S0960-894X(14)00778-1. doi:, 10.1016/j.bmcl.2014.07.054. PMID:25086681[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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