title: Functional insights from a comparative study on the dynamics of Antigen85 proteins and MPT51 from Mycobacterium tuberculosis.
abstract: Antigen85 (Ag85) proteins of Mycobacterium tuberculosis are mycolyl transferases that aid in cell wall biosynthesis. MPT51 (Ag85D) is closely related to Ag85 proteins. We have performed a comparative molecular dynamics (MD) simulation study of Ag85 proteins (Ag85A, Ag85B, and Ag85C) and MPT51. We observe that helix α5, β7-α9 loop, and N-terminal region of helix α9 of Ag85 proteins are mobile, suggestive of lid like movement over the active site. Further, in Ag85B, we observe the proposed scooting mode of the hydrophobic gating residue Phe232. Our simulations also show a similar scooting mode for Phe232 of Ag85A and Trp158 of Ag85C. We also found aromatic residue clusters at the ends of the hydrophobic channel of Ag85 proteins, which may have functional significance. Although MPT51 lacks the tunnel, it has the aromatic clusters. The aromatic cluster region has the ability to bind trehalose. From an immunoinformatics study, a promiscuous linear epitope was identified in MPT51 which could be useful in subunit vaccine studies. Recent studies have shown that a mycobacterial protein HupB, interacts with Ag85 proteins and has a regulatory role in cell wall biogenesis, with implications in growth rate and latency. We performed molecular docking studies of HupB protein with Ag85 proteins and predicted potential sites of interaction in Ag85 proteins. The insights gained through the current study can potentially pave way for newer therapeutic interventions. Graphical Abstract Dynamics of antigen85 proteins and MPT51 from Mycobacterium tuberculosis.
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, 600025, India.
authors.forename: Shobana
authors.initials: S
authors.lastname: Sundar
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, 600025, India.
authors.forename: David
authors.initials: D
authors.lastname: Annaraj
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, 600025, India.
authors.forename: Anitha
authors.initials: A
authors.lastname: Selvan
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, 600025, India.
authors.forename: Pallavi Guha
authors.initials: PG
authors.lastname: Biswas
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, 600025, India.
authors.forename: Reshma
authors.initials: R
authors.lastname: Vijayakumaran
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, 600025, India. sharmi.anishetty@gmail.com.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Anishetty
mesh_terms: D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C082911:MPT51 protein, Mycobacterium; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; C121433:antigen 85B, Mycobacterium tuberculosis; C119774:antigen 85C, Mycobacterium tuberculosis
keywords: Antigen85; Aromatic cluster; HupB; Immunoinformatics; MPT51; Molecular dynamics simulation