Allosteric regulation and substrate activation in cytosolic nucleotidase II from Legionella pneumophila

摘要: Cytosolic nucleotidase II (cN-II) from Legionella pneumophila (Lp) catalyzes the hydrolysis of GMP and dGMP displaying sigmoidal curves, whereas catalysis IMP displayed a biphasic curve in initial rate versus substrate concentration plots. Allosteric modulators mammalian cN-II did not activate LpcN-II although GTP, GDP were specific activators. Crystal structures tetrameric revealed an activator-binding site at dimer interface. A double mutation this allosteric-binding abolished activation, confirming structural observations. The acting as activator, partitioning between allosteric active site, is basis for sigmoidicity velocity plot. tetramer showed differences subunit organization upon activator binding that are absent activator-bound human structure. This first observation change induced by may be molecular mechanism enzyme activation. Database The coordinates structure factors reported paper have been submitted to Protein Data Bank under accession numbers 2BDE 4G63. number complexed 4OHF. Structured digital abstract LpcN-II and LpcN-II bind by molecular sieving (View interaction) LpcN-II and LpcN-II bind by x-ray crystallography (View interaction) [Structured abstract was added on 5 March 2014 after original online publication]