@article {153398, title = {Computational analysis of the effect of a binding protein (RbpA) on the dynamics of Mycobacterium tuberculosis RNA polymerase assembly.}, journal = {PLoS One}, volume = {20}, year = {2025}, month = {2025}, pages = {e0317187}, abstract = {

BACKGROUND: RNA polymerase-binding protein A (RbpA) is an actinomycetes-specific protein crucial for the growth and survival of the pathogen Mycobacterium tuberculosis. Its role is essential and influences the transcription and antibiotic responses. However, the regulatory mechanisms underlying RbpA-mediated transcription remain unknown. In this study, we employed various computational techniques to investigate the role of RbpA in the formation and dynamics of the RNA polymerase complex.

RESULTS: Our analysis reveals significant structural rearrangements in RNA polymerase happen upon interaction with RbpA. Hotspot residues, crucial amino acids in the RbpA-mediated transcriptional regulation, were identified through our examination. The study elucidates the dynamic behavior within the complex, providing insights into the flexibility and functional dynamics of the RbpA-RNA polymerase interaction. Notably, potential allosteric mechanisms, involving the interface of subunits α1 and α2 were uncovered, shedding light on how RbpA modulates transcriptional activity.

CONCLUSIONS: Finally, potential ligands meant for the α1-α2 binding site were identified through virtual screening. The outcomes of our computational study serve as a foundation for experimental investigations into inhibitors targeting the RbpA-regulated dynamics in RNA polymerase. Overall, this research contributes valuable information for understanding the intricate regulatory networks of RbpA in the context of transcription and suggests potential avenues for the development of RbpA-targeted therapeutics.

}, keywords = {Bacterial Proteins, Binding Sites, DNA-Directed RNA Polymerases, Molecular Dynamics Simulation, Mycobacterium tuberculosis, Protein Binding, Transcription, Genetic}, issn = {1932-6203}, doi = {10.1371/journal.pone.0317187}, url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0317187}, author = {Bheemireddy, Sneha and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {908, title = {Enriching the annotation of Mycobacterium tuberculosis H37Rv proteome using remote homology detection approaches: insights into structure and function.}, journal = {Tuberculosis (Edinb)}, volume = {95}, year = {2015}, month = {2015 Jan}, pages = {14-25}, abstract = {

The availability of the genome sequence of Mycobacterium tuberculosis H37Rv has encouraged determination of large numbers of protein structures and detailed definition of the biological information encoded therein; yet, the functions of many proteins in M. tuberculosis remain unknown. The emergence of multidrug resistant strains makes it a priority to exploit recent advances in homology recognition and structure prediction to re-analyse its gene products. Here we report the structural and functional characterization of gene products encoded in the M. tuberculosis genome, with the help of sensitive profile-based remote homology search and fold recognition algorithms resulting in an enhanced annotation of the proteome where 95\% of the M. tuberculosis proteins were identified wholly or partly with information on structure or function. New information includes association of 244 proteins with 205 domain families and a separate set of new association of folds to 64 proteins. Extending structural information across uncharacterized protein families represented in the M. tuberculosis proteome, by determining superfamily relationships between families of known and unknown structures, has contributed to an enhancement in the knowledge of structural content. In retrospect, such superfamily relationships have facilitated recognition of probable structure and/or function for several uncharacterized protein families, eventually aiding recognition of probable functions for homologous proteins corresponding to such families. Gene products unique to mycobacteria for which no functions could be identified are 183. Of these 18 were determined to be M. tuberculosis specific. Such pathogen-specific proteins are speculated to harbour virulence factors required for pathogenesis. A re-annotated proteome of M. tuberculosis, with greater completeness of annotated proteins and domain assigned regions, provides a valuable basis for experimental endeavours designed to obtain a better understanding of pathogenesis and to accelerate the process of drug target discovery.

}, keywords = {Hydrolases, Mycobacterium tuberculosis, Protein Structure, Tertiary, Proteome, Sequence Analysis, Protein, Structural Homology, Protein}, issn = {1873-281X}, doi = {10.1016/j.tube.2014.10.009}, author = {Ramakrishnan, Gayatri and Ochoa-Monta{\~n}o, Bernardo and Raghavender, Upadhyayula S and Mudgal, Richa and Joshi, Adwait G and Chandra, Nagasuma R and Sowdhamini, Ramanathan and Blundell, Tom L and Srinivasan, Narayanaswamy} }