1vsn

Crystal structure of a potent small molecule inhibitor bound to cathepsin K

spinqualitylabelsall models 1vsn, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1vsn is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 2fdz. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NFT Gene: CTSK, CTSO, CTSO2 (HUMAN) Activity: Cathepsin K, with EC number 3.4.22.38 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [CATK_HUMAN] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature. Function [CATK_HUMAN] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. 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 Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of cathepsin K inhibitor, further optimization led to identification of compound 22 (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This compound showed excellent pharmacokinetics and efficacy in an ovariectomized (OVX) rhesus monkey model. The volumes of distribution close to unity were consistent with this compound not being lysosomotropic, which is a characteristic of basic cathepsin K inhibitors. Identification of a potent and selective non-basic cathepsin K inhibitor.,Li CS, Deschenes D, Desmarais S, Falgueyret JP, Gauthier JY, Kimmel DB, Leger S, Masse F, McGrath ME, McKay DJ, Percival MD, Riendeau D, Rodan SB, Therien M, Truong VL, Wesolowski G, Zamboni R, Black WC Bioorg Med Chem Lett. 2006 Apr 1;16(7):1985-9. Epub 2006 Jan 18. PMID:16413777 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cathepsin 3D structures

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