Abstract

Background: Mycobacterium tuberculosis (MTB), the primary etiological agent of human tuberculosis (TB), is one of nine closely related species within the MTB complex (MTBC). Notwithstanding progress in infection management, there is currently desires for novel, efficacious TB medications that diminish infections. This study used a hypothetical protein BBW91_01090 (Accession: OHO21781, 271 Amino acids) for structural and functional analysis.
Methods: The hypothetical MTB protein was used for structural and functional analysis, with its subcellular localization and physicochemical characteristics suggesting it is periplasmic, soluble, and stable. Effective annotation tools such as InterProScan, SUPERFAMILY, and NCBI-CD Search have classified our target protein as Type VII Secretion System L, D Transpeptidase. ITASSER homology modelling revealed a three-dimensional structure mostly characterized by random coils, which were stabilized by YASARA energy minimization. The TM score over 0.5 indicated robust structural alignment, and validation tools (ERRAT, QMEAN, Verify3D, PROCHECK) confirmed its reliability. PyMOL and CASTp identified the active site. Penicillin G and Penicillin V ligands exhibited equivalent binding affinities and essential interaction residues for the target protein in molecular docking studies.
Results: The predicted protein is identified as a periplasmic, soluble, and stable type VII secretion system L, D-transpeptidase. The 3D model predominantly exhibited random coils, attaining a TM score exceeding 0.5, indicating a dependable structural alignment. The quality of the structure has been confirmed by validation tools. Docking studies demonstrated that penicillin G and V bind effectively to the active site. Additionally, comparative analysis indicated the lack of human homologs, highlighting its potential as a specific drug target.
Conclusions: The study identifies a unique and structurally stable MTB protein with no human homologs, potentially exploitable as a drug target. The research facilitates prospective therapeutic endeavors. The recent research may facilitate the development of inhibitors for antibiotic-resistant MTB.

Key words: Mycobacterium tuberculosis; hypothetical protein; in silico characterization; L, D- transpeptidases; Penicillin Binding Proteins.