Figure 3.

Inhibition of ADAMTS-7 cleavage of ATS7FP7 by TIMP-4, JG23, and EDV33. ADAMTS-7 was incubated for 1 h either at 5 nM with TIMP-4 (A), JG23 (B) or EDV33 (C) at 10 nM before addition of ATS7FP7 (40 μM). Percent of inhibition was calculated from control reactions containing only DMSO. For TIMP-4, data were fitted to the Morrison equation, while in case of JG23 or EDV33 the IC₅₀ equation was used. The data are presented as average ± SEM (n = 3). Structures of TIMP-4, JG23 and EDV33 are shown above the graphs. In (A), the model of TIMP-4 was generated using homology modelling with HHpred and MODELLER. The N-terminal domain is shown in pink, the C-terminal domain in blue. Residues that sit in the active site of metalloproteases are shown as sticks with carbon in green. From left to right: Cys¹⁰² disulphide bonded to Cys³⁰ (first residue in the mature protein), Ser³¹-Pro³⁴. Chelated Zinc (Zn²⁺) in the active site of metalloproteases is shown as a blue sphere.