4obz

Structure of Cathepsin D with inhibitor 2-(3,4-dimethoxyphenyl)-N-[N-(4-methylbenzyl)carbamimidoyl]acetamide

spinqualitylabelsall models 4obz, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4obz is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: 2S4, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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. 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cathepsin 3D structures

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