Abstract:
Mycobacterium tuberculosis is a well-known pathogen due to the emergence of drug resistance
associated with it, where transcriptional regulators play a key role in infection, colonization
and persistence. The genome of M. tuberculosis encodes many transcriptional regulators, and here we
report an in-depth in silico characterization of a GntR regulator: MoyR, a possible monooxygenase
regulator. Homology modelling provided a reliable structure for MoyR, showing homology with a
HutC regulator DasR from Streptomyces coelicolor. In silico physicochemical analysis revealed that
MoyR is a cytoplasmic protein with higher thermal stability and higher pI. Four highly probable binding
pockets were determined in MoyR and the druggability was higher in the orthosteric binding site
consisting of three conserved critical residues: TYR179, ARG223 and GLU234. Two highly conserved
leucine residues were identified in the effector-binding region of MoyR and other HutC homologues,
suggesting that these two residues can be crucial for structure stability and oligomerization. Virtual
screening of drug leads resulted in four drug-like compounds with greater affinity to MoyR with
potential inhibitory effects for MoyR. Our findings support that this regulator protein can be valuable
as a therapeutic target that can be used for developing drug leads.
