Figure 2.

Structure of the catalytic and ubiquitin-associated (UBA) domain of MARK. (A) Cα trace of the inactive catalytic domain of MARK with carboxy-terminal extension, in the inactive apo state. The nucleotide binding site is marked by an ATP molecule represented by transparent spheres (grey). The catalytic domain is drawn in blue (amino-terminal lobe) and purple (carboxy-terminal lobe) except for the P-loop (cyan) and the T-loop or activation loop (including its amino-terminal anchor; yellow). The drawing is based on the coordinates of MARK1 [PDB: 2HAK] [23]. The activation segment is variable and, in most cases, partially invisible in the crystal structures. Two complete conformations of the T-loop are shown in superposition; these correspond to molecules E and F of the MARK1 crystal structure. The carboxy-terminal extension of the catalytic domain comprises the common docking (CD) site and linker (pale green and green) and the UBA domain (red), which binds to the amino-terminal-lobe, at the rear side of the active site. (B) Top: Overlay of the UBA domain of MARK1 (red) and that of HHR23A (light blue) [PDB: 1IFY] [38]. Bottom: schematic drawing showing the orientation of the helices in both structures. The carboxy-terminal helix (alpha3) of the UBA domain in MARK is inverted compared to the conventional orientation exemplified by HHR23A. The figure was generated with PyMOL [39].