Abstract:
Tuberculosis is one of the most common diseases that causes many deaths around the world. As a result of the continuous evolution of Mycobacterium tuberculosis, some novel strains
show high resistance to most anti-TB drug therapies. Antibiotic resistance associated with
Mycobacterium tuberculosis can be resolved by the development of anti-virulence drug
targets. The MarR gene family is one of the major transcriptional regulation families in
Mycobacterium tuberculosis, and this family mainly contributes to controlling several
bacterial responses, such as bacterial virulence. The regulator Rv 3095 which was identified
as a virulence gene regulator, mainly regulates the expression of Rv 3096 gene that codes for
a putative xylanase enzyme. The main objective of this study is to determine the structure
and active site of the putative xylanase enzyme. Molecular docking was conducted to identify
possible antibiotic ligands that can block the active site of putative xylanase enzyme. The
FASTA sequence of Rv 3096 was downloaded from the NCBI database, and the structure of
the protein was predicted by using alpha fold and Robetta fold protein prediction servers. The active site of the Rv 3096 protein was determined by using CoachD active site prediction
server. The molecular docking was done by using PyRx software, and ligand libraries were
downloaded from the Zinc 15 database. The structure of the N-terminal end of the protein
was predicted by both protein prediction servers with high confidence levels. However, both
protein prediction servers were unable to predict the structure of the C-terminal end of the
protein with high confidence levels. The pocket which has the highest C score is considered
an active site of the predicted protein. In the virtual screening, the highest binding affinities to
the active site of the xylanase enzyme were recorded by drug ligands that belong to the
penicillin and doxycycline drug groups.
