4S1H

Pyridoxal kinase of Entamoeba histolytica with ADP

Summary for 4S1H

• Entry DOI: 10.2210/pdb4s1h/pdb
• Related: 4S1I
• Descriptor: Pyridoxal kinase, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: pyridoxal 5'-phosphate, transferase
• Biological source: Entamoeba histolytica
• Total number of polymer chains: 2
• Total formula weight: 65143.54

Authors

Tarique, K.F.,Devi, S.,Abdul Rehman, S.A.,Gourinath, S. (deposition date: 2015-01-13, release date: 2015-01-28, Last modification date: 2024-04-03)

Primary citation

Tarique, K.F.,Devi, S.,Tomar, P.,Ali, M.F.,Rehman, S.A.A.,Gourinath, S.
Characterization and functional insights into the Entamoeba histolytica pyridoxal kinase, an enzyme essential for its survival.
J.Struct.Biol., 212:107645-107645, 2020

PubMed Abstract: Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B 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 B 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 Bde-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.

PubMed: 33045383
DOI: 10.1016/j.jsb.2020.107645

Experimental method

X-RAY DIFFRACTION (1.6 Å)