Structural and functional annotation of hypothetical proteins of human adenovirus: prioritizing the novel drug targets

Naveed, Muhammad; Tehreem, Sana; Usman, Muhammad; Chaudhry, Zoma; Abbas, Ghulam

doi:10.1186/s13104-017-2992-z

Cited by 22 publications

(18 citation statements)

References 51 publications

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“…In previous studies, the annotation of hypothetical proteins (proteins with unknown functions) was successfully relied on to predict protein structure and function [19,20]. Therefore, the putative function of the conserved hypothetical protein (Ts_04814) (accession no.…”

Section: Sequence and Bioinformatics Analysismentioning

confidence: 99%

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

et al. 2020

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Trichinella spiralis can modulate host immune responses to retain a suitable environment for its long-term survival. Incidentally, the parasite elicits regulatory effects through immunomodulatory molecule release, which can suppress host inflammation and may be used for the treatment of unrelated inflammatory diseases in someday. Here we identified and characterized a novel T. spiralis cystatin (TsCstN), which inhibits inflammation mediated by LPS-treated macrophages.Proteins contained in the excretory-secretory (ES) product of muscle-stage T. spiralis (ES-L1) were fractionated, and each was treated with mouse bone marrow-derived macrophages (mBMDMs) before LPS stimulation. The fractions that exhibited high immunomodulatory property by decreasing pro-inflammatory cytokines or increasing anti-inflammatory cytokines were identified by mass spectrometry. Incidentally, the conserved hypothetical protein (Tsp_04814) was selected for further characterization as it presented the most significant MS score. An annotation of Tsp_04814 using protein structural homology comparison suggested that it has high structural similarity to human cystatin E/M (TM score 0.690). The recombinant T. spiralis novel cystatin (rTsCstN) was expressed in Escherichia coli at a molecular weight of approximately 13 kDa. Mouse anti-rTsCstN polyclonal antibody (pAb) could detect native TsCstN in crude worm antigens (CWA) and ES-L1 and be predominantly localized in the stichosome and subcuticular cells. rTsCstN inhibited cysteine proteases in vitro, especially cathepsin L, at an optimal pH of 6. Besides, rTsCstN could be internalized into mBMDMs, which were mostly distributed in the cytoplasm and lysosome both before and after LPS stimulation. To evaluate the rTsCstN immunomodulatory properties on mBMDMs, rTsCstN was incubated with mBMDM before LPS stimulation; this demonstrated that rTsCstN suppressed pro-inflammatory cytokine production and MHC class II expression.T. spiralis L1-derived TsCstN was characterized as a novel cysteine PLOS NEGLECTED TROPICAL DISEASES

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Section: Sequence and Bioinformatics Analysismentioning

confidence: 99%

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

et al. 2020

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“…The crystallization of hypothetical proteins to identify clues from the protein structure is another potential method. Readers can refer to recent work on the discovery of hypothetical proteins [168,169,170,171]. The numbers of hypothetical proteins will expand rapidly as more underexplored genomes are sequenced; however, the speed to understand proteins’ functions remain sluggish [53].…”

Section: Limitations and Future Directions Of Prokaryote Discoverymentioning

confidence: 99%

Current Status and Potential Applications of Underexplored Prokaryotes

et al. 2019

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Thousands of prokaryotic genera have been published, but methodological bias in the study of prokaryotes is noted. Prokaryotes that are relatively easy to isolate have been well-studied from multiple aspects. Massive quantities of experimental findings and knowledge generated from the well-known prokaryotic strains are inundating scientific publications. However, researchers may neglect or pay little attention to the uncommon prokaryotes and hard-to-cultivate microorganisms. In this review, we provide a systematic update on the discovery of underexplored culturable and unculturable prokaryotes and discuss the insights accumulated from various research efforts. Examining these neglected prokaryotes may elucidate their novelties and functions and pave the way for their industrial applications. In addition, we hope that this review will prompt the scientific community to reconsider these untapped pragmatic resources.

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“…According to Muhammad Naveed et al, 50-60% of genes has a known function in most of the completely sequenced genomes. The number of genes having unknown functions called hypothetical proteins are present in each organism's genome [14]. In other words, hypothetical proteins are a category of the protein whose existence is not proved by any experimental evidence but can be portended to be expressed from an open reading frame (ORF) [15].…”

Section: Introductionmentioning

confidence: 99%

Functional annotation of an ecologically important protein from Chloroflexus aurantiacus involved in polyhydroxyalkanoates (PHA) biosynthetic pathway

Rahman¹,

Susmi²,

Yasmin³

et al. 2020

SN Appl. Sci.

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Chloroflexus aurantiacus J-10-fI strain is a thermophilic gram-negative bacterium that possesses many proteins in its genome; some are considered as hypothetical proteins. The use of bioinformatics tools can assist in understanding this organism through structural and functional annotation. Our study aimed to assign structure and function to an ecologically important hypothetical protein present in the bacterial genome. To analyze the hypothetical protein (WP_012259469.1), we used an in silico approach to find out various properties like physiochemical characteristics, subcellular localization, 3D structure, protein-protein interaction and functional annotation. Protein-protein interactions were obtained from the STRING database. In silico analysis revealed that the protein is a soluble protein with predominantly alpha-helices in its secondary structure. The 3D model of the protein has been found to be novel and possessed expected quality as assessed by several quality assessment tools. Functional annotation indicated that the protein acted like a (R)-specific enoyl-CoA hydratase which is linked with PHA synthesis. Protein-protein interactions also showed with high confidence that the protein interacted with a protein synthesizer of enoyl-CoA hydratase involved in PHA biosynthesis. Polyhydroxyalkanoate (PHA) is a novel polyester used as a biodegradable thermoplastic and plays a crucial role in environmental biodegradability and biocompatibility. An extensive variety of microorganisms produces PHA for intracellular carbon and energy storage purposes. In the present investigation, we bioinformatically confirmed that the WP_012259469.1 is associated with the PHA biosynthesis pathway. From our anaylses, we also predict that polyhydroxyalkanoate (PHAs) has the potential to become an alternative source of renewable and biodegradable polyesters.

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Structural and functional annotation of hypothetical proteins of human adenovirus: prioritizing the novel drug targets

Cited by 22 publications

References 51 publications

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

Current Status and Potential Applications of Underexplored Prokaryotes

Functional annotation of an ecologically important protein from Chloroflexus aurantiacus involved in polyhydroxyalkanoates (PHA) biosynthetic pathway

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