Browsing by Author "Jebasingh Tennyson"

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Identification of inhibitors for the collagenase of Leptospira interrogans through docking and molecular simulation
(Springer Nature, 2025) Vikram Kumar; Selvaa Kumar Chellasamy; Nagesh Srikakulam; P. K. Satheeshkumar; Madathiparambil Gopalakrishnan Madanan; Jebasingh Tennyson
Leptospirosis is a neglected tropical zoonotic infection caused by Leptospira interrogans. Collagenase protein is a virulence factor for pathogenic L. interrogans, which facilitates its invasion into Homo sapiens. There is a paucity of chemical compounds that can inhibit the colonisation and infiltration of the pathogen into the host. We looked at the modelled collagenase from L. interrogans for docking studies with ligands and simulations in this study. Based on the results, 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one, obtained from Musella lasiocarpa (Chinese Dwarf Banana) basically a nutraceuticals and terpene deoxyherqueinone from tea plants and Penicillium herquei was identified as having drug-like properties and demonstrated better binding within the active site pocket of collagenase during the course of protein–ligand docking and simulation. This selected phytochemical can be further taken up for wet-lab-based validation to provide a potential drug to curb this waterborne disease in the near future. © Indian National Science Academy 2024.
Identification of inhibitors for the collagenase of Leptospira interrogans through docking and molecular simulation
(Springer Nature, 2024) Vikram Kumar; Selvaa Kumar Chellasamy; Nagesh Srikakulam; Padikara K. Satheeshkumar; Madanan Gopalakrishnan Madathiparambil; Jebasingh Tennyson
Leptospirosis is a neglected tropical zoonotic infection caused by Leptospira interrogans. Collagenase protein is a virulence factor for pathogenic L. interrogans, which facilitates its invasion into Homo sapiens. There is a paucity of chemical compounds that can inhibit the colonisation and infiltration of the pathogen into the host. We looked at the modelled collagenase from L. interrogans for docking studies with ligands and simulations in this study. Based on the results, 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one, obtained from Musella lasiocarpa (Chinese Dwarf Banana) basically a nutraceuticals and terpene deoxyherqueinone from tea plants and Penicillium herquei was identified as having drug-like properties and demonstrated better binding within the active site pocket of collagenase during the course of protein–ligand docking and simulation. This selected phytochemical can be further taken up for wet-lab-based validation to provide a potential drug to curb this waterborne disease in the near future. © Indian National Science Academy 2024.
Proteomic approach and expression analysis revealed the differential expression of predicted leptospiral proteases capable of ECM degradation
(Elsevier B.V., 2018) Gunasekaran Dhandapani; Thoduvayil Sikha; Sneha M. Pinto; M. Kiran Kumar; Krishna Patel; Manish Kumar; Vikram Kumar; Jebasingh Tennyson; P.K. Satheeshkumar; Harsha Gowda; T.S. Keshava Prasad; M.G. Madanan
Leptospira, the causative agent of leptospirosis is known to have many proteases with potential to degrade extracellular matrix. However, a multipronged approach to identify, classify, characterize and elucidate their role has not been attempted. Our proteomic approach using high-resolution LC-MS/MS analysis of Triton X-114 fractions of Leptospira interrogans resulted in the identification of 104 proteases out of 130 proteases predicted by MEROPS. In Leptospira approximately 3.5% of the genome complements for proteases, which include catalytic types of metallo-, serine-, cysteine-, aspartic-, threonine- and asparagine- peptidases. Comparison of proteases from different serovars revealed that M04, M09B, M14A, M75, M28A, A01 and U73 protease families are exclusively present in pathogenic form. The M23 and S33 protease families are represented with >14 members in Leptospira. The differential expression under physiological temperature (37 °C) and osmolarity (300 mOsM) showed that proteases belonging to the catalytic type of Metallo-peptidases are upregulated significantly in pathogenic conditions. In silico prediction and characterization of the proteases revealed that several proteases are membrane anchored and secretory, classical as well as non-classical system. The study demonstrates the diversity and complexity of proteases, while maintaining conservation across the serovars in Leptospira and their differential expression under pathogenic conditions. © 2018 Elsevier B.V.
Triton X-114 Fractionated Subcellular Proteome of Leptospira interrogans Shows Selective Enrichment of Pathogenic and Outer Membrane Proteins in the Detergent Fraction
(Wiley-VCH Verlag, 2020) Sikha Thoduvayil; Gunasekaran Dhandapani; Rahul Brahma; Rex Devasahayam Arokia Balaya; Kiran K. Mangalaparthi; Krishna Patel; Manish Kumar; Jebasingh Tennyson; P.K. Satheeshkumar; Mahesh J. Kulkarni; Sneha M. Pinto; T. S. Keshava Prasad; Madathiparambil G. Madanan
The Triton X-114-based solubilization and temperature-dependent phase separation of proteins is used for subcellular fractionation where, aqueous, detergent, and pellet fractions represents cytoplasmic, outer membrane (OM), and inner membrane proteins, respectively. Mass spectrometry-based proteomic analysis of Triton X-114 fractions of proteomic analysis of Leptospira interrogans identified 2957 unique proteins distributed across the fractions. The results are compared with bioinformatics predictions on their subcellular localization and pathogenic nature. Analysis of the distribution of proteins across the Triton X-114 fractions with the predicted characteristics is performed based on “number” of unique type of proteins, and “quantity” which represents the amount of unique protein. The highest number of predicted outer membrane proteins (OMPs) and pathogenic proteins are found in aqueous and pellet fractions, whereas detergent fraction representing the OM has the highest quantity of OMPs and pathogenic proteins though lower in number than the aqueous and pellet fractions. This leaves the possibility of an upsurge in pathogenic proteins and OMPs on the OM under pathogenic conditions suggesting their potential use to combat leptospirosis. Further, the Triton X-114 subcellular fractions are more correlated to enrichment of pathogenic proteins predicted by MP3 software than predicted localization. © 2020 Wiley-VCH GmbH