Aggrecanase

Aggrecanases are extracellular proteolytic enzymes that are members of the ADAMTS (A Disintegrin And Metalloprotease with Thrombospondin Motifs) 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-1^[1] and ADAMTS5 or aggrecanase-2.^[2] Both proteins contain thrombospondin (TS) motifs required for proper recognition of substrates.^[3] Although both proteins can cleave the substrate aggrecan at the same position, they differ in kinetics and in secondary cleavage sites.^[4]

References[]

^ Tortorella, MD; Burn, TC; Pratta, MA; Abbaszade, I; Hollis, JM; Liu, R; Rosenfeld, SA; Copeland, RA; et al. (1999). "Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins". Science. 284 (5420): 1664–6. doi:10.1126/science.284.5420.1664. PMID 10356395.
^ Abbaszade, I; Liu, RQ; Yang, F; Rosenfeld, SA; Ross, OH; Link, JR; Ellis, DM; Tortorella, MD; et al. (1999). "Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family". J Biol Chem. 274 (33): 23443–50. doi:10.1074/jbc.274.33.23443. PMID 10438522.
^ 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. 275 (33): 25791–7. doi:10.1074/jbc.M001065200. PMID 10827174.
^ 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. doi:10.1016/S0945-053X(02)00069-0. PMID 12392761.

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[Tortorella-1] Tortorella, MD; Burn, TC; Pratta, MA; Abbaszade, I; Hollis, JM; Liu, R; Rosenfeld, SA; Copeland, RA; et al. (1999). "Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins". Science. 284 (5420): 1664–6. doi:10.1126/science.284.5420.1664. PMID 10356395.

[Abbaszade-2] Abbaszade, I; Liu, RQ; Yang, F; Rosenfeld, SA; Ross, OH; Link, JR; Ellis, DM; Tortorella, MD; et al. (1999). "Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family". J Biol Chem. 274 (33): 23443–50. doi:10.1074/jbc.274.33.23443. PMID 10438522.

[TortorellaPratta-3] 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. 275 (33): 25791–7. doi:10.1074/jbc.M001065200. PMID 10827174.

[TortorellaLiu-4] 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. doi:10.1016/S0945-053X(02)00069-0. PMID 12392761.

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v t Proteases: metalloendopeptidases (EC 3.4.24)
ADAM proteins	Alpha secretases ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
Matrix metalloproteinases	Collagenases MMP1 MMP8 Gelatinases MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
Other	Neprilysin Procollagen peptidase Thermolysin Pregnancy-associated plasma protein A Bone morphogenetic protein 1 Lysostaphin Insulin-degrading enzyme ZMPSTE24

v t Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)