Interaction of Aldehyde dehydrogenase with acetaminophen as examined by spectroscopies and molecular docking

Abstract

The interaction of acetaminophen, a non-substrate anionic ligand, with Aldehyde Dehydrogenase was studied by fluorescence, UV–Vis absorption, and circular dichroism spectroscopies under simulated physiological conditions. The fluorescence spectra and data generated showed that acetaminophen binding to ALDH is purely dynamic quenching mechanism. The acetaminophen-ALDH is kinetically rapid reversible interaction with a binding constant, Ka, of 4.91×103 L mol−1. There was an existence of second binding site of ALDH for acetaminophen at saturating acetaminophen concentration. The binding sites were non-cooperative. The thermodynamic parameters obtained suggest that Van der Waal force and hydrogen bonding played a major role in the binding of acetaminophen to ALDH. The interaction caused perturbation of the ALDH structures with an obvious reduction in the α-helix. The binding distance of 4.43 nm was obtained between Acetaminophen and ALDH. Using Ficoll 400 as macro-viscosogen and glycerol as micro-viscosogen, Stoke-Einstein empirical plot demonstrated that acetaminophen-ALDH binding was diffusion controlled. Molecular docking showed the participation of some amino acids in the complex formation with −5.3 kcal binding energy. With these, ALDH might not an excipient detoxifier of acetaminophen but could be involved in its pegylation/encapsulation.

Investigating Paracetamol’s Role as a Potential Treatment for Parkinson’s Disease: Ab Initio Analysis of Dopamine, l-DOPA, Paracetamol, and NAPQI Interactions with Enzymes Involved in Dopamine Metabolism

“…This result is consistent with the experimental work of Courade et al, who showed that paracetamol in concentration of up to 100 mM had no effect on MAO(A) activity. 34 Kolawole showed experimentally and via docking simulations that paracetamol does bind to ALDH, 39 and in fact, our work also shows that both paracetamol and NAPQI should be competitive inhibitors for ALDH, with EBEs stronger than natural substrates DOPAL and homovanilin. Inhibition of ALDH may thus cause a shift in equilibrium, which would indirectly inhibit MAO.…”

Understanding the in silico aspects of bacterial catabolic cascade for styrene degradation

“…Few reports have been published discussing the molecular docking of aldehyde dehydrogenases to different substrates showing similar binding energy. For instance, the docking of aldehyde dehydrogenase to an aromatic drug, acetaminophen, into its hydrophobic cavity involving isoleucine, phenylalanine, arginine, leucine, glutamic acid, and glutamine via hydrogen and Van der Waals bonding showed quite similar binding energy (−5.3 kcal mol −1 ) 66 . Although, aldehyde dehydrogenases have well‐established involvement in polyaromatic hydrocarbons, studies specifically concentrated on PAD involvement in styrene metabolism are still emerging 67 …”