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The Unusual Nucleotide Recognition Properties of the Resistance Enzyme ANT(4′): Inorganic Tri/Polyphosphate as a Substrate for Aminoglycoside Inactivation
Author(s) -
Revuelta Julia,
Corzana Francisco,
Bastida Agatha,
Asensio Juan Luis
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201000641
Subject(s) - polyphosphate , enzyme , aminoglycoside , nucleotide , substrate (aquarium) , chemistry , biochemistry , substrate specificity , computational biology , biology , gene , antibiotics , ecology , phosphate
A pocket of resistance : We have analysed the molecular determinants for nucleotide recognition by the resistance enzyme ANT(4′). Our results demonstrate that its binding epitope is restricted to the inorganic triphosphate fragment. Strikingly, this, together with longer polyphosphate oligomers, can be employed as cosubstrates in aminoglycoside inactivation (see figure), implying a change in the normal activity of the enzyme. These results have implications in the design of specific enzymatic inhibitors.