We investigated the identification of a protein target using the hydroxynaphthoic acid ligand (1-hydroxi-2-naphthoic acid), a small biologically active molecule. The compound has shown antimicrobial properties against Staphylococcus aureus in previous studies, underscoring the importance of discovering and characterizing its protein targets to gain insights into the mechanisms underlying its therapeutic effect. Using affinity chromatography, we were able to detect a protein of approximately 25 kDa that binds to the ligand N-(4-aminobutyl)-1-hydroxy-2-naphthamide. This was followed by isolation and analysis by mass spectrometry (MS). We succeeded in identifying NAD(P)H dehydrogenase (quinone), also known as WrbA, as a potential target of our small molecule. The enzyme plays a key role in the respiratory chain of the bacterial cell, where it maintains the balance of redox processes and is actively involved in the formation of a microbial biofilm. These crucial functions make it the centerpiece of the bacterial stress response. Blocking or inhibiting the action of NAD(P)H dehydrogenase therefore appears to be a promising approach for antimicrobial activity.
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