Structural and functional implications of the hexokinase-nickel interaction.
The interaction between nickel and yeast hexokinase was studied. The binding of nickel showed a positive cooperativity, and saturation was not reached. The nickel binding induced modifications in the secondary structure of the protein; thus, a lost of alpha helix and beta turns, as well as an increase of the random structure and beta sheet was observed. The monomer/dimmer equilibrium of the protein was modified in the presence of nickel, and the monomer state was mainly obtained at the highest nickel concentrations studied. These changes on the protein structure caused a decrease in the enzyme activity. According to kinetic studies, nickel caused a non-competitive inhibition when glucose was the variable substrate and a linear competitive inhibition when ATP was the variable substrate.
Romero
C S
CS
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Olmo
R
R
Teijón
C
C
Blanco
M D
MD
Teijón
J M
JM
Romero
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D002942:Circular Dichroism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000633:toxicity; D005947:Glucose / Q000378:metabolism; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D009532:Nickel / Q000633:toxicity*; D020836:Protein Structure, Quaternary / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013053:Spectrophotometry
D004791:Enzyme Inhibitors; D009532:Nickel; D000255:Adenosine Triphosphate; D006593:Hexokinase; D005947:Glucose