Characterization and functional insights into the Entamoeba histolytica pyridoxal kinase, an enzyme essential for its survival

Khaja Faisal Tarique, Suneeta Devi, Priya Tomar, Mohammad Farhan Ali, Syed Arif Abdul Rehman, Samudrala Gourinath (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B6 and a cofactor for more than 140 enzymes. This coenzyme plays a pivotal role in catalysis of various enzymatic reactions that are critical for the survival of organisms. Entamoeba histolytica depends on the uptake of pyridoxal (PL), a B6 vitamer from the external environment which is then phosphorylated by pyridoxal kinase (EhPLK) to form PLP via the salvage pathway. E. histolytica cannot synthesise vitamin B6de-novo, and also lacks pyridoxine 5'-phosphate oxidase, a salvage pathway enzyme required to produce PLP from pyridoxine phosphate (PNP) and pyridoxamine phosphate (PMP). Analysing the importance of PLK in E. histolytica, we have determined the high-resolution crystal structures of the dimeric pyridoxal kinase in apo, ADP-bound, and PLP-bound states. These structures provided a snapshot of the transition state and help in understanding the reaction mechanism in greater detail. The EhPLK structure significantly differed from the human homologue at its PLP binding site, and the phylogenetic study also revealed its divergence from human PLK. Further, gene regulation of EhPLK using sense and antisense RNA showed that any change in optimal level is harmful to the pathogen. Biochemical and in vivo studies unveiled EhPLK to be essential for this pathogen, while the molecular differences with human PLK structure can be exploited for the structure-guided design of EhPLK inhibitors.

Original languageEnglish
Article number107645
Number of pages13
JournalJournal of Structural Biology
Issue number3
Early online date9 Oct 2020
Publication statusPublished - 1 Dec 2020


  • Binding Sites/physiology
  • Catalysis
  • Entamoeba histolytica/metabolism
  • Phosphorylation/physiology
  • Phylogeny
  • Pyridoxal Kinase/metabolism
  • Pyridoxal Phosphate/analogs & derivatives
  • Pyridoxamine/analogs & derivatives
  • Pyridoxaminephosphate Oxidase/metabolism
  • Vitamin B 6/metabolism


Dive into the research topics of 'Characterization and functional insights into the Entamoeba histolytica pyridoxal kinase, an enzyme essential for its survival'. Together they form a unique fingerprint.

Cite this