Aggrecanase

Aggrecanases are proteolytic enzymes that are members of the ADAM protein (A Disintegrin And Metalloprotease) family. Aggrecanases act on large proteoglycans known as aggrecans, which are components of connective tissues such as cartilage. The inappropriate activity of aggrecanase is a mechanism by which cartilage degradation occurs in diseases such as arthritis. At least two forms of aggrecanase exist in humans: ADAMTS4 or aggrecanase-1Tortorella MD et al. (1999). Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. "Science" 284(5420):1664-6. PMID 10356395 ] and ADAMTS11 or aggrecanase-2.Abbaszade I et al. (1999). Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family. "J Biol Chem" 274(33):23443-50. PMID 10438522] Both proteins contain thrombospondin (TS) motifs required for proper recognition of substrates.Tortorella M, Pratta M, Liu RQ, Abbaszade I, Ross H, Burn T, Arner E. (2000). The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage. "J Biol Chem" 75(33):25791-7. PMID 10827174 ] Although both proteins can cleave the substrate aggrecan at the same position, they differ in kinetics and in secondary cleavage sites.Tortorella MD, Liu RQ, Burn T, Newton RC, Arner E. (2002). Characterization of human aggrecanase 2 (ADAM-TS5): substrate specificity studies and comparison with aggrecanase 1 (ADAM-TS4). "Matrix Biol" 21(6):499-511. PMID 12392761]

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