Drug Design: Principles and Applications by Abhinav Grover

Author:Abhinav Grover
Language: eng
Format: epub
Publisher: Springer Singapore, Singapore

6.4.9 Phosphofructokinase

Phosphofructokinase (Pfk) is the enzyme which is involved in the glycolytic pathway and located in glycosomes. The enzymes which are involved in glycolytic pathway are mostly conserved, but Pfk is not that much conserved and it shows the variability in different species. There are two types of Pfks: first one is ATP-dependent while another is PPi-dependent Pfk. PPi dependent undergoes modification, binds with different ligands, and then it provides the chance to know the difference between humans and parasitic enzymes; it gives the information to design a drug based on structure.

Pfk of L. donovani and L. braziliensis is allosteric in nature, and when it binds with the substrate, it requires AMP for the activation. The inhibition process will be reversed by the activator, AMP [62]. ATP Pfk contains glycine residue at the position of 124 where as in kinetoplastids contains lysine at that position. The substitution of lysine residue by glycine did not show any different effect in enzyme activity in L. donovani Pfk, but it shows the effect in T.brucie, so they mentioned that the mutation creates effect on the behavior of the enzyme Pfk [63].

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