Molecular Docking Study of Catecholamines and [4-(Propan-2-yl) Phenyl]Carbamic acid with Tyrosine Hydroxylase

Abstract

Parkinson’s disease is a major age-related neurodegenerative disorder. As the classical disease-related motor symptoms are associated with the loss of dopamine-generating cells within the substantia nigra, tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines has become an important target in the development of Parkinson’s disease drug candidates, with the focus to augment TH levels or its activity. By contrast, TH inhibitors are of relevance in the treatment of conditions associated with catecholamine over-production, as occurs in pheochromocytomas. To aid characterizing new drug candidates, a molecular docking study of catecholamines and a novel hypothetical compound [4-(propan-2-yl) phenyl]carbamic acid (PPCA) with TH is described. Docking was performed using Autodock4.2 and results were analyzed using Chimera1.5.2. All the studied ligands were found to bind within a deep narrow groove lined with polar aromatic and acidic residues within TH. Our results corroborated a ‘hexa interacting amino acids unit’ located in this deep narrow groove crucial to the interaction of PPCA and the studied catecholamines with TH, whereby the ‘His361-His336 dyad’ was found to be even more crucial to these binding interactions. PPCA displayed a binding interaction with human TH that was comparable to the original TH substrate, L-tyrosine. Hence PPCA may warrant in vitro and in vivo characterization with TH to assess its potential as a candidate therapeutic.

Influence of Catecholamines (Epinephrine/Norepinephrine) on Biofilm Formation and Adhesion in Pathogenic and Probiotic Strains of Enterococcus faecalis

“…These results are consistent with our data, as we found that the binding energy value of the interaction between Epi and VicK ex (WalK ex ) is −4.08. This data is also in agreement with the study of Parveen et al (2012) , which have indicated values of −4.56 Kcal/mol for Epi. In the same paper, the binding energy between NE and its receptor was measured to be −8.56 Kcal/mol, a value significantly different from our result.…”

“…For phentolamine and propanolol, the two clusters found are relatively the same, so we can suggest that these two molecules can interact with our putative adrenergic sensor VicK (WalK) and be blockers of the sensor. The values of the interaction energy of NE, Epi and propanolol are very close as we find in our study and in the literature ( Parveen et al, 2012 ; Dimić et al, 2020 ). This leads to think that these three molecules may have the same affinity for VicK (WalK).…”

“…In the same paper, the binding energy between NE and its receptor was measured to be −8.56 Kcal/mol, a value significantly different from our result. This difference is probably explained by the fact that NE provided the best binding affinity with human Tyrosine hydroxylase ( Parveen et al, 2012 ). For phentolamine and propanolol, the two clusters found are relatively the same, so we can suggest that these two molecules can interact with our putative adrenergic sensor VicK (WalK) and be blockers of the sensor.…”