In-Silico Characterization of a Hypothetical Protein, Rv1288 of Mycobacterium tuberculosis Containing an Esterase Signature and an Uncommon LytE Domain

Kumar, Arbind; Maan, Pratibha; Singh, Gurpreet; Kaur, Jagdeep

doi:10.2174/1573409912666161124144725

Cited by 3 publications

(5 citation statements)

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“…Lyt domain is known to interact with the peptidoglycan moiety of cell wall (Buist et al, 2008). Molecular docking studies also demonstrated that it could bind to the N-acetyl glucosamine moiety of peptidoglycan (Kumar et al, 2017a). The peptidoglycan binding assay suggested that Rv1288 was attached to the cell wall of M.tb by Lyt domain.…”

Section: Discussionmentioning

confidence: 99%

“…Kumar et al, performed the bioinformatics analysis by homology modeling and molecular docking to study the probable role of this protein in M.tb . It was suggested as a probable lipolytic enzyme by in silico experiments (Takayama et al, 2005; Kumar et al, 2017a). The LytE domain was predicted to be responsible for the binding of this protein with mycobacterial cell wall.…”

Section: Introductionmentioning

confidence: 99%

“…Esterase domain showed the presence of HGGG tetrapeptide motif, GxSxG pentapeptide sequence and S294, D391 and H425 as catalytic triad. Further docking studies predicted the high binding affinity of serine hydrolase inhibitors such as THL and PMSF with this enzyme (Kumar et al, 2017a). However, all these properties were annotated on the basis of bioinformatics and prediction methods and needed to be validated by wet lab experiments.…”

Section: Introductionmentioning

confidence: 99%

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Rv1288, a Two Domain, Cell Wall Anchored, Nutrient Stress Inducible Carboxyl-Esterase of Mycobacterium tuberculosis, Modulates Cell Wall Lipid

Maan

Kumar

Kaur

2018

Front. Cell. Infect. Microbiol.

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Rv1288, a conserved hypothetical protein of M. tuberculosis (M.tb), was recently characterized as two-domain esterase enzyme by in silico study. In the present study, Rv1288 and its domains (Est and Lyt) were cloned individually from M.tb into E. coli for expression and purification. The purified rRv1288 and rEst proteins exhibited lipolytic activity with medium chain length esters as optimum substrates, while Lyt domain did not show enzymatic activity. However, presence of Lyt domain resulted in enhanced rate of protein aggregation at higher temperature. Both rRv1288 and rEst followed the similar patterns of substrate specificity, temperature and pH activity. Site directed mutagenesis confirmed the Ser-294, Asp-391 and His-425 as catalytic site residues. Rv1288 was found to be present in cell wall fraction of M.tb H37Ra. Peptidoglycan binding activity of Rv1288 and its domains demonstrated that the Lyt domain is essential for anchoring protein to the cell wall. Expression of rv1288 was up regulated in M.tb under nutrient starved condition. Over expression of rv1288 in surrogate host M. smegmatis led to change in colony morphology, enhanced pellicle and aggregate formation that might be linked with the changed lipid composition of bacterial cell wall. Cell wall of M. smegmatis expressing rv1288 had higher amount of lipids, with a significant increase in trehalose dimycolate content. Rv1288 also leads to increase in drug resistance of M. smegmatis. Rv1288 also enhanced the intracellular survival of M. smegmatis in Raw264.7 cell line. Overall, this study suggested that Rv1288, a cell wall localized carboxyl hydrolase with mycolyl-transferase activity, modulated the cell wall lipids to favor the survival of bacteria under stress condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rv1288, a Two Domain, Cell Wall Anchored, Nutrient Stress Inducible Carboxyl-Esterase of Mycobacterium tuberculosis, Modulates Cell Wall Lipid

Maan

Kumar

Kaur

2018

Front. Cell. Infect. Microbiol.

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“…A recent bioinformatic analysis of the M. tuberculosis genome identified an esterase associated with an N‐terminal domain containing three LysM modules that could help position the enzyme in the cell wall (Kumar, Maan, Singh, & Kaur, 2017), but no experimental data have yet to support this hypothesis. Only two other examples of Corynebacteriales cell wall binding proteins have been described so far.…”

Section: Discussionmentioning

confidence: 99%

The C‐terminal domain of Corynebacterium glutamicum mycoloyltransferase A is composed of five repeated motifs involved in cell wall binding and stability

Dietrich

Sierra-Gallay

Masi

et al. 2020

Molecular Microbiology

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Bacterial cell envelopes are essential complex structures involved in morphology, resistance to environmental stress, signal transduction and transport of solutes and macromolecules. These basic physiological functions are assumed by cell envelope proteins, which can include adhesins and virulence factors in the case of pathogenic species. Proteins present in bacterial cell envelopes are either directly associated with the membranes, for example, transmembrane proteins and lipoproteins, or bound to specific polysaccharidic components of the cell wall, including peptidoglycan (PGN) and cell wall secondary polymers (CWSPs). For instance, many proteins of monoderm Gram-positive bacteria are covalently linked to the PGN by a transpeptidation reaction, which is catalyzed by enzymes

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“…For the ve in silico tools and servers, ROC analysis revealed a high level of dependability and credibility (Kumar et al, 2017). When two or more tools predicted the same result for HP33, the con dence of prediction was judged high.…”

Section: Evaluation Of Performancementioning

confidence: 98%

Homo-oligomer models prediction, functional characterization, and Ab initio docking analysis of hypothetical protein HP33 from Vibrio harveyi strain

Islam

Sanjida

Mou

et al. 2022

Preprint

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It is reported that antigenicity of a unique hypothetical protein named HP33 of Vibrio harveyi Y6 strain causes scale drop and muscle necrosis disease (SDMND) in Lates calcarifer. This distinct protein was found from only V. harveyi SDMND and is responsible for 40-50% mortality. Despite these devastating complications, there is still no cure or vaccine for the disease. As a result, the current work sought to elucidate the roles of HP33 protein. The sequence similarity was searched across the available bioinformatics databases to find the homologous protein. This hypothetical protein is known to be an unstable, nonpolar, and outer membrane protein based on its subcellular localization and physicochemical properties. Functional annotation tools predicted our target protein has only a single domain. The random coil was found to be predominant in the secondary structure. Quality evaluation methods were used to predict and confirm the secondary and tertiary structure. After YASARA energy minimization, the 3D structure became more stable, which was confirmed by many quality assessment methods. Additionally, the active site and interacting proteins were examined. An important biological activity of the HP is that it contains single functional domains that may be responsible for representing a biosynthetic gene cluster. In addition, protein-ligand docking analysis showed two possible drug molecules against HP33 pathogenesis. Finally, the homo-oligomers models prediction and ab-initio docking results will provide good insights for further immunological study which might be of significant relevance to future V. harveyi genetics research.

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In-Silico Characterization of a Hypothetical Protein, Rv1288 of Mycobacterium tuberculosis Containing an Esterase Signature and an Uncommon LytE Domain

Abstract: In the present investigation, we bioinformatically confirmed that Rv1288 is most likely a LytE domain containing lipolytic enzyme showing similarity to hormone sensitive lipases/esterases.

Cited by 3 publications

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Rv1288, a Two Domain, Cell Wall Anchored, Nutrient Stress Inducible Carboxyl-Esterase of Mycobacterium tuberculosis, Modulates Cell Wall Lipid

Rv1288, a Two Domain, Cell Wall Anchored, Nutrient Stress Inducible Carboxyl-Esterase of Mycobacterium tuberculosis, Modulates Cell Wall Lipid

The C‐terminal domain of Corynebacterium glutamicum mycoloyltransferase A is composed of five repeated motifs involved in cell wall binding and stability

Homo-oligomer models prediction, functional characterization, and Ab initio docking analysis of hypothetical protein HP33 from Vibrio harveyi strain

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