Figure 2

Structural comparison of four netrin domain-containing proteins. The netrin domains of Ac-TMP-2 (homology model based on Hs-TIMP-2), Hs-TIMP-2 (PDB accession code 1br9), AceES-2 (PDB accession code 3nsw) and Sh-TIMP (A_01727; homology model based on Hs-TIMP-2) are coloured blue, cysteine side chain residues are rendered as yellow sticks. Red highlighted areas indicate regions of interactions with MMPs; these regions are inferred for Ac-TMP-2, AceES-2 and Sh-TIMP based on the alignment in Figure 1. The parasite proteins Ac-TMP-2 and Sh-TIMP and human Hs-TIMP-2 share the same intra-domain disulphide bonding pattern. In contrast, AceES-2 possesses a different pattern with two intra-molecular disulphide bonds. The disulphide bond engaging the N-terminal cysteine (Cys3-Cys62) is reminiscent of that found in Ac-TMP-2, Sh-TIMP and Hs-TIMP-2. The other disulphide bond (Cys77-Cys84) is unique to AceES-2. The C-terminal domain of Hs-TIMP-2 is rendered magenta. The C-terminal domains of Ac-TMP-2 and Sh-TIMP are shown in grey for illustration only and the three-dimensional structures of these domains are neither based on computational nor experimental evidence. Comparative modelling was performed using MODELLER [59] based on the structure-based sequence alignment shown in Figure 1.