3ljt

Crystal Structure of the Catalytic Domain of ADAMTS-5 in Complex with an Amino-2-indanol compound

spinqualitylabelsall models 3ljt, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ljt is a 1 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 1.6Å Ligands: CA, EDO, LA3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ATS5_HUMAN Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. May play a role in proteolytic processing mostly during the peri-implantation period. 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 A ((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl) succinamide derivative (here referred to as Compound 12) shows significant activity toward many matrix metalloproteinases (MMPs), including MMP-2, MMP-8, MMP-9, and MMP-13. Modeling studies had predicted that this compound would not bind to ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) due to its shallow S1' pocket. However, inhibition analysis revealed it to be a nanomolar inhibitor of both ADAMTS-4 and -5. The observed inconsistency was explained by analysis of crystallographic structures, which showed that Compound 12 in complex with the catalytic domain of ADAMTS-5 (cataTS5) exhibits an unusual conformation in the S1' pocket of the protein. This first demonstration that cataTS5 can undergo an induced conformational change in its active site pocket by a molecule like Compound 12 should enable the design of new aggrecanase inhibitors with better potency and selectivity profiles. Structure analysis reveals the flexibility of the ADAMTS-5 active site.,Shieh HS, Tomasselli AG, Mathis KJ, Schnute ME, Woodard SS, Caspers N, Williams JM, Kiefer JR, Munie G, Wittwer A, Malfait AM, Tortorella MD Protein Sci. 2011 Apr;20(4):735-44. doi: 10.1002/pro.606. PMID:21370305 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also A Disintegrin And Metalloproteinase 3D structures Superoxide dismutase 3D structures

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