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.