Fig. 1: Overview of TG2 conformational changes and the existing active site inhibitors. | Communications Biology

Fig. 1: Overview of TG2 conformational changes and the existing active site inhibitors.

From: Distinct conformational states enable transglutaminase 2 to promote cancer cell survival versus cell death

Fig. 1

a GDP or GTP bind to TG2 in a closed state (PDB: 1KV3, GDP shown in yellow). Calcium or active site inhibitors bind TG2 in an open conformation (b) (PDB: 2Q3Z, peptide inhibitor in maroon) that is crosslinking active. The drug binding site in (c) is highlighted with a solid box (red) to indicate it is accessible. Numerous studies have suggested that the closed state of TG2 promotes cell survival while the open state is cytotoxic through an unknown mechanism. The N-terminal β-sandwich domain is colored orange, the catalytic domain is colored green, and the β-barrels are colored cyan (β-barrel 1) and blue (β-barrel 2). c Docking pose of TTGM 5826 and a peptidomimetic inhibitor in the active site of TG2 (d) Ligand interaction diagrams of the peptidomimetic inhibitor (top) and TTGM5826 (bottom) with TG2.

Back to article page