Exploiting Unique Structural and Functional Properties of Malarial Glycolytic Enzymes for Antimalarial Drug Development

Figure 2

Unique structural differences between PfGAPDH and HsGAPDH. (a) Tetrameric structure of PfGAPDH (PDB ID: 2B4R). NAD-binding domain (Rossman fold) is shown in grey and catalytic domain is shown in cyan with S-loop shown in blue (i). Zoomed image of PfGAPDH showing the residues Ser-193 and His-42 that are unable to make hydrogen bonds (ii). (b) Tetrameric structure of HsGAPDH (PDB ID: 1ZNQ). NAD-binding domain is shown in grey and catalytic domain is shown in cyan with S-loop shown in blue (i). Zoomed image of HsGAPDH showing the hydrogen bonding between residues Ser-192 and His-42 (ii). (c) Alignment of single subunits of PfGAPDH and HsGAPDH. NAD-binding domains of PfGAPDH and HsGAPDH are shown in green and cyan, respectively, and catalytic domains of PfGAPDH and HsGAPDH are shown in blue and magenta, respectively. Bound NAD is shown in orange. PfGAPDH loop containing the Lys-Gly insert (shown as sticks in blue) constricts the opening of the NAD-binding cavity more as compared to the HsGAPDH loop (shown as sticks in magenta). Structures were visualized by molecular visualization software PyMOL (DeLano Scientific).

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