Fig. 4.

Proximity relation of loop1 with loop2 and the flexible loop. The top box is a cartoon representation of the closed-holo-pkDDC dimer (Pdb id: 1js6) illustrating the proximity relation of loop1 (Cyan) with loop2 (Gray) and the flexible loop (Black) of the partner monomer. The three domains are colored as in Fig. 1. In this structure, loop1 (Cyan) directly interacts with loop2′ (Gray) which in turn contacts the flexible loop3′ (Black). The position of some important residues of loop1 in the holo state (i.e. Tyr-79 and Trp-71) and the position of the two aromatic stacking interactions (Phe-80 with Tyr-274 and Trp-304 of the large domain and of Phe-77 with Phe-388 and Phe-448 from the C-domain) is also shown. Notice that in the structure of the open-apo-form of hDDC (bottom box), due to the separation of the two subunits, the residues of loop2 and of the flexible loop are not visible, and only the aromatic stacking interaction with the residues of the C-domain is conserved.