Enzyme domain interactions

Kato, M., Miyazawa, K., and Kitamuea, N. a deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP, J Biol Chem, 2000, 275, 37481-7. 

Figure 1 The mode of action for bacterial AB-type exotoxins. AB-toxins are enzymes that modify specific substrate molecules in the cytosol of eukaryotic cells. Besides the enzyme domain (A-domain), AB-toxins have a binding/translocation domain (B-domain) that specifically interacts with a cell-surface receptor and facilitates internalization of the toxin into cellular transport vesicles, such as endosomes. In many cases, the B-domain mediates translocation of the A-domain into the cytosol by pore formation in cellular membranes. By following receptor-mediated endocytosis, AB-type toxins exploit normal vesicle traffic pathways into cells. One type of toxin escapes from early acidified endosomes (EE) into the cytosol, thus they are referred to as short-trip-toxins . In contrast, the long-trip-toxins take a retrograde route from early endosomes (EE) through late endosomes (LE), trans-Golgi network (TGN), and Golgi apparatus into the endoplasmic reticulum (ER) from where the A-domains translocate into the cytosol to modify specific substrates.

The overall structure of these metalloproteins is characterized by a deep active site cleft that divides the molecule into two domains, with the catalytically active zinc located at the bottom of the active site in the center of the molecule (Fig. 3). The structures of protein-inhibitor complexes [15,17,19-26] representing different families, indicate that the PI residue [37] is the principal recognition element for these enzymes (Fig. 5). Inhibitors bound to members of the matrixin family [17,19-23,25] adopt an extended conformation (Fig. 6), with the side chain at the P2 subsite directed away from the enz5mie on the opposite side of the inhibitor backbone to the PI specificity pocket. In addition to the zinc ligands, there are essential enzyme-inhibitor interactions between backbone atoms of the protein and complementary atoms of the inhibitor 1. 

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