Pentavalent ions dependency is a conserved property of adenosine kinase from diverse sources: identification of a novel motif implicated in phosphate and magnesium ion binding and substrate inhibition

Biochemistry
M C MajRadhey S Gupta

Abstract

The catalytic activity of adenosine kinase (AK) from mammalian sources has previously been shown to exhibit a marked dependency upon the presence of pentavalent ions (PVI), such as phosphate (PO4), arsenate, or vanadate. We now show that the activity of AK from diverse sources, including plant, yeast, and protist species, is also markedly enhanced in the presence of PVI. In all cases, PO4 or other PVI exerted their effects primarily by decreasing the Km for adenosine and alleviating the inhibition caused by high concentrations of substrates. These results provide evidence that PVI dependency is a conserved property of AK and perhaps of the PfkB family of carbohydrate kinases which includes AK. On the basis of sequence alignments, we have identified a conserved motif NXXE within the PfkB family. The N and E of this motif make close contacts with Mg2+ and PO4 ions in the crystal structures of AK and bacterial ribokinase (another PfkB member which shows PVI dependency), implicating these residues in their binding. Site-directed mutagenesis of these residues in Chinese hamster AK have resulted in active proteins with greatly altered phosphate stimulation and substrate inhibition characteristics. The N239Q mutation leads to the form...Continue Reading

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Citations

Jan 31, 2006·Molecular and Cellular Biochemistry·Jae ParkRadhey S Gupta
Nov 22, 2011·Acta Crystallographica. Section D, Biological Crystallography·Yoshiaki YasutakeTomohiro Tamura
Nov 5, 2003·Journal of Bacteriology·Mary C LongWilliam B Parker
Jun 10, 2009·FEBS Letters·Jae ParkRadhey S Gupta
Jun 24, 2009·IUBMB Life·Victoria Guixé, Felipe Merino
Nov 20, 2012·Proteins·Sarah R ElkinLinda Columbus
Oct 5, 2010·Archives of Biochemistry and Biophysics·Jaime Andrés Rivas-PardoVictoria Guixé
Mar 10, 2015·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Diego Quiroga-RogerVictoria Guixé
Aug 12, 2018·Scientific Reports·Renata Rocha de OliveiraKleber Gomes Franchini
Apr 18, 2013·Pharmacological Reviews·Detlev Boison
Jan 3, 2008·The Journal of Biological Chemistry·Munender VodnalaAnders Hofer
Dec 6, 2019·Chembiochem : a European Journal of Chemical Biology·Richard DemmlerDirk Hoffmeister
Jan 3, 2020·Journal of Chemical Information and Modeling·Igor Barden GrilloGerd Bruno Rocha

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