4oc6: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4oc6 is ON HOLD
+==Structure of Cathepsin D with inhibitor 2-bromo-N-[(2S,3S)-4-{[2-(2,4-dichlorophenyl)ethyl][3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]amino}-3-hydroxy-1-(3-phenoxyphenyl)butan-2-yl]-4,5-dimethoxybenzamide==
+<StructureSection load='4oc6' size='340' side='right'caption='[[4oc6]], [[Resolution|resolution]] 2.64&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4oc6]] is a 2 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=4OC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OC6 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.64&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2S1:2-BROMO-N-[(2S,3S)-4-{[2-(2,4-DICHLOROPHENYL)ETHYL][3-(1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)PROPANOYL]AMINO}-3-HYDROXY-1-(3-PHENOXYPHENYL)BUTAN-2-YL]-4,5-DIMETHOXYBENZAMIDE'>2S1</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=4oc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oc6 OCA], [https://pdbe.org/4oc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oc6 RCSB], [https://www.ebi.ac.uk/pdbsum/4oc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oc6 ProSAT]</span></td></tr>
+</table>
+== 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 ==
+[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;">
+== Publication Abstract from PubMed ==
+We 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.
-Authors: Graedler, U., Czodrowski, P., Tsaklakidis, C., Klein, M., Maskos, K., Leuthner, B.
+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<ref>PMID:25086681</ref>
-Description: Structure-based optimization of non-peptidic Cathepsin D inhibitors
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4oc6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Czodrowski P]]
+[[Category: Graedler U]]
+[[Category: Klein M]]
+[[Category: Leuthner B]]
+[[Category: Maskos K]]
+[[Category: Tsaklakidis C]]