Proteins with Distinct Sites for Different Functions in More Than One Domain
The second category of moonlighting proteins are multidomain proteins (listed in Table 2.2) which utilize functional sites in separate domains for carrying out their primary and moonlighting function(s).
Figure 2.5 Human MAPK1/ERK2. The MAPK1 active site is shown in blue and the DNA-binding motif is highlighted in red. Different domains are shown in gray and orange (PDB:4G6N). (See color plate section for the color representation of this figure.)
Malate synthase, Mycobacterium tuberculosis
Malate synthase (EC 188.8.131.52) is a cytoplasmic enzyme (Function 1) involved in the glyoxalate pathway . In M. tuberculosis it has also been found on the cell wall, adapted to function as an adhesin that binds laminin and fibrinogen which may contribute to M. tuberculosis virulence by promoting infection and dissemination (Function 2) . The structure of the M. tuberculosis malate synthase consists of two identical chains each of which consists of four domains: an a-orthogonal bundle, a TIM barrel, a mainly p complex domain, and an a up-down bundle . The malate synthase active site residues are Glu273, Asp274, Arg339, Glu434, Leu461, Asp462, and Glu633 (highlighted as blue sticks) and the residues that are associated with binding laminin or fibrinogen are Gln696-Glu727 (highlighted in red) (Fig. 2.6). Both the sites are present in different domain regions of the protein.