scholarly journals Prioritizing functional phosphorylation sites based on multiple feature integration

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Qingyu Xiao ◽  
Benpeng Miao ◽  
Jie Bi ◽  
Zhen Wang ◽  
Yixue Li
Keyword(s):  
Biological Activities ◽  
Feature Integration ◽  
Phosphorylation Sites ◽  
Post Translational Modification ◽  
Functional Sites ◽  
Tyrosine Residues ◽  
Functional Studies ◽  
Multiple Feature ◽  
Different Types ◽  
Mass Spectrometric Techniques

Abstract Protein phosphorylation is an important type of post-translational modification that is involved in a variety of biological activities. Most phosphorylation events occur on serine, threonine and tyrosine residues in eukaryotes. In recent years, many phosphorylation sites have been identified as a result of advances in mass-spectrometric techniques. However, a large percentage of phosphorylation sites may be non-functional. Systematically prioritizing functional sites from a large number of phosphorylation sites will be increasingly important for the study of their biological roles. This study focused on exploring the intrinsic features of functional phosphorylation sites to predict whether a phosphosite is likely to be functional. We found significant differences in the distribution of evolutionary conservation, kinase association, disorder score, and secondary structure between known functional and background phosphorylation datasets. We built four different types of classifiers based on the most representative features and found that their performances were similar. We also prioritized 213,837 human phosphorylation sites from a variety of phosphorylation databases, which will be helpful for subsequent functional studies. All predicted results are available for query and download on our website (Predict Functional Phosphosites, PFP, http://pfp.biosino.org/pfp).

Computational prediction and analysis of species-specific fungi phosphorylation via feature optimization strategy

2018 ◽  
Vol 21 (2) ◽  
pp. 595-608 ◽  
Author(s):  
Man Cao ◽  
Guodong Chen ◽  
Jialin Yu ◽  
Shaoping Shi
Keyword(s):  
Protein Phosphorylation ◽  
Computational Prediction ◽  
Optimization Method ◽  
Phosphorylation Sites ◽  
Optimization Strategy ◽  
Post Translational Modification ◽  
Tyrosine Residues ◽  
Identification Of Fungi ◽  
Feature Optimization ◽  
Species Specific

Abstract Protein phosphorylation is a reversible and ubiquitous post-translational modification that primarily occurs at serine, threonine and tyrosine residues and regulates a variety of biological processes. In this paper, we first briefly summarized the current progresses in computational prediction of eukaryotic protein phosphorylation sites, which mainly focused on animals and plants, especially on human, with a less extent on fungi. Since the number of identified fungi phosphorylation sites has greatly increased in a wide variety of organisms and their roles in pathological physiology still remain largely unknown, more attention has been paid on the identification of fungi-specific phosphorylation. Here, experimental fungi phosphorylation sites data were collected and most of the sites were classified into different types to be encoded with various features and trained via a two-step feature optimization method. A novel method for prediction of species-specific fungi phosphorylation-PreSSFP was developed, which can identify fungi phosphorylation in seven species for specific serine, threonine and tyrosine residues (http://computbiol.ncu.edu.cn/PreSSFP). Meanwhile, we critically evaluated the performance of PreSSFP and compared it with other existing tools. The satisfying results showed that PreSSFP is a robust predictor. Feature analyses exhibited that there have some significant differences among seven species. The species-specific prediction via two-step feature optimization method to mine important features for training could considerably improve the prediction performance. We anticipate that our study provides a new lead for future computational analysis of fungi phosphorylation.

scholarly journals Erratum: Corrigendum: Prioritizing functional phosphorylation sites based on multiple feature integration

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Qingyu Xiao ◽  
Benpeng Miao ◽  
Jie Bi ◽  
Zhen Wang ◽  
Yixue Li
Keyword(s):  
Feature Integration ◽  
Phosphorylation Sites ◽  
Multiple Feature

Prediction of Nitration Sites Based on FCBF Method and Stacking Ensemble Model

2021 ◽  
Vol 18 ◽  
Author(s):  
Min Liu ◽  
Lu Zhang ◽  
Xinyi Qin ◽  
Tao Huang ◽  
Ziwei Xu ◽  
...  
Keyword(s):  
Prediction Model ◽  
Protein Sequence ◽  
Cross Validation ◽  
Transplant Rejection ◽  
Sampling Technique ◽  
Single Type ◽  
Post Translational Modification ◽  
Tyrosine Residues ◽  
Under Sampling ◽  
Fusion Features

Background: Nitration is one of the important Post-Translational Modification (PTM) occurring on the tyrosine residues of proteins. The occurrence of protein tyrosine nitration under disease conditions is inevitable and represents a shift from the signal transducing physiological actions of -NO to oxidative and potentially pathogenic pathways. Abnormal protein nitration modification can lead to serious human diseases, including neurodegenerative diseases, acute respiratory distress, organ transplant rejection and lung cancer. Objective: It is necessary and important to identify the nitration sites in protein sequences. Predicting that which tyrosine residues in the protein sequence are nitrated and which are not is of great significance for the study of nitration mechanism and related diseases. Methods: In this study, a prediction model of nitration sites based on the over-under sampling strategy and the FCBF method was proposed by stacking ensemble learning and fusing multiple features. Firstly, the protein sequence sample was encoded by 2701-dimensional fusion features (PseAAC, PSSM, AAIndex, CKSAAP, Disorder). Secondly, the ranked feature set was generated by the FCBF method according to the symmetric uncertainty metric. Thirdly, in the process of model training, use the over- and under- sampling technique was used to tackle the imbalanced dataset. Finally, the Incremental Feature Selection (IFS) method was adopted to extract an optimal classifier based on 10-fold cross-validation. Results and Conclusion: Results show that the model has significant performance advantages in indicators such as MCC, Recall and F1-score, no matter in what way the comparison was conducted with other classifiers on the independent test set, or made by cross-validation with single-type feature or with fusion-features on the training set. By integrating the FCBF feature ranking methods, over- and under- sampling technique and a stacking model composed of multiple base classifiers, an effective prediction model for nitration PTM sites was build, which can achieve a better recall rate when the ratio of positive and negative samples is highly imbalanced.

scholarly journals Potential Phosphorylation of Viral Nonstructural Protein 1 in Dengue Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1393
Author(s):  
Thanyaporn Dechtawewat ◽  
Sittiruk Roytrakul ◽  
Yodying Yingchutrakul ◽  
Sawanya Charoenlappanit ◽  
Bunpote Siridechadilok ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Antiviral Drug ◽  
Denv Infection ◽  
Site Directed Mutagenesis ◽  
Phosphorylation Sites ◽  
Post Translational Modification ◽  
Multifunctional Protein ◽  
Nonstructural Protein 1 ◽  
Underlying Mechanisms

Dengue virus (DENV) infection causes a spectrum of dengue diseases that have unclear underlying mechanisms. Nonstructural protein 1 (NS1) is a multifunctional protein of DENV that is involved in DENV infection and dengue pathogenesis. This study investigated the potential post-translational modification of DENV NS1 by phosphorylation following DENV infection. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), 24 potential phosphorylation sites were identified in both cell-associated and extracellular NS1 proteins from three different cell lines infected with DENV. Cell-free kinase assays also demonstrated kinase activity in purified preparations of DENV NS1 proteins. Further studies were conducted to determine the roles of specific phosphorylation sites on NS1 proteins by site-directed mutagenesis with alanine substitution. The T27A and Y32A mutations had a deleterious effect on DENV infectivity. The T29A, T230A, and S233A mutations significantly decreased the production of infectious DENV but did not affect relative levels of intracellular DENV NS1 expression or NS1 secretion. Only the T230A mutation led to a significant reduction of detectable DENV NS1 dimers in virus-infected cells; however, none of the mutations interfered with DENV NS1 oligomeric formation. These findings highlight the importance of DENV NS1 phosphorylation that may pave the way for future target-specific antiviral drug design.

scholarly journals Snail mucus from the mantle and foot of two land snails, Lissachatina fulica and Hemiplecta distincta, exhibits different protein profile and biological activity

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nattaphop Noothuan ◽  
Kantamas Apitanyasai ◽  
Somsak Panha ◽  
Anchalee Tassanakajon
Keyword(s):  
Biological Activities ◽  
Protein Pattern ◽  
Protein Profile ◽  
Antibacterial Properties ◽  
Biological Properties ◽  
Specific Protein ◽  
Land Snails ◽  
Snail Species ◽  
Significant Difference ◽  
Different Types

Abstract Objective Snails secrete different types of mucus that serve several functions, and are increasingly being exploited for medical and cosmetic applications. In this study, we explored the protein pattern and compared the biological properties of the mucus secreted from the mantle collar and foot of two snail species, Lissachatina fulica and Hemiplecta distincta. Result Protein profile showed a different pattern between the two species and between the two secretory parts. The mantle-specific protein bands were further characterized and among them was an antibacterial protein, achacin. Accordingly, the mucus from the mantle exhibited the higher antibacterial activity than that from the foot in both snail species. The mucus from H. distincta, first reported here, also showed antibacterial properties, but with a lower activity compared to that for L. fulica. Snail mucus also exhibited anti-tyrosinase activity and antioxidant activity but with no significant difference between the foot and mantle mucus. These results indicate some different protein compositions and biological activities of snail slime from the mantle and foot, which might be associated with their specific functions in the animal and are useful for medical applications.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

Interactions between cell growth-regulating domains in the products of the adenovirus E1A oncogene

1988 ◽  
Vol 8 (4) ◽  
pp. 1756-1764
Author(s):  
B Moran ◽  
B Zerler
Keyword(s):  
Dna Synthesis ◽  
Biological Activities ◽  
Rat Kidney ◽  
Kidney Cells ◽  
Transient Expression Assay ◽  
Focus Formation ◽  
Mutant Proteins ◽  
Functional Sites ◽  
Adenovirus E1a ◽  
Cellular Dna

Among the various biological activities expressed by the products of the adenovirus E1A gene are the abilities to induce cellular DNA synthesis and proliferation in quiescent primary baby rat kidney cells. The functional sites for these activities lie principally within two regions of the E1A proteins: an N-terminal region and a small second region of approximately 20 amino acids further downstream. To study the biological functions of the first domain, we constructed an in-frame deletion of amino acid positions 23 through 107 of the E1A products. This deletion did not impede the ability of the E1A products to transactivate the adenovirus early region 3 promoter in a transient-expression assay in HeLa cells. The ability to induce DNA synthesis in quiescent baby rat kidney cells was, however, lost in the absence of these sequences. Deletion of the small second region induced a form of S phase in which DNA synthesis occurred in the apparent absence of controls required for the cessation of DNA synthesis and progression through the remainder of the cell cycle. These cells did not appear to accumulate in or before G2, and many appeared to have a DNA content greater than that in G2. The functions of both domains are required for production of transformed foci in a ras cooperation assay. Focus formation occurred, however, even when the two domains were introduced on two separate plasmids. This complementation effect appeared to require expression of both of the mutant proteins and did not appear to result merely from recombination at the DNA level.

Semisynthetic triazoles as an approach in the discovery of Novel Lead Compounds

2021 ◽  
Vol 25 ◽  
Author(s):  
Pedro Alves Bezerra Morais ◽  
Carla Santana Francisco ◽  
Heberth de Paula ◽  
Rayssa Ribeiro ◽  
Mariana Alves Eloy ◽  
...  
Keyword(s):  
Natural Products ◽  
Medicinal Chemistry ◽  
Chemical Space ◽  
Biological Activities ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Modern Drug ◽  
New Chemical Entities ◽  
Almost All ◽  
The 19Th Century

: Historically, the medicinal chemistry is concerned with the approach of organic chemistry to new drug synthesis. Considering the fruitful collections of new molecular entities, the dedicated efforts for medicinal chemistry are rewarding. Planning and search of new and applicable pharmacologic therapies involve the altruistic nature of the scientists. Since the 19th century, notoriously the application of isolated and characterized plant-derived compounds in modern drug discovery and in various stages of clinical development highlight its viability and significance. Natural products influence a broad range of biological processes, covering transcription, translation, and post-translational modification and being effective modulators of almost all basic cellular processes. The research of new chemical entities through “click chemistry” continuously opens up a map for the remarkable exploration of chemical space in towards leading natural products optimization by structure-activity relationship. Finally, here in this review, we expect to gather a broad knowledge involving triazolic natural products derivatives, synthetic routes, structures, and their biological activities.

scholarly journals Non3 is an essential Drosophila gene required for proper nucleolus assembly

2019 ◽  
Vol 23 (2) ◽  
pp. 190-198
Author(s):  
E. N. Andreyeva ◽  
A. A. Ogienko ◽  
A. A. Yushkova ◽  
J. V. Popova ◽  
G. A. Pavlova ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Large Deletion ◽  
Protein Product ◽  
P Element ◽  
Post Translational Modification ◽  
Allelic Series ◽  
Larval Brain ◽  
Functional Studies ◽  
Mild Reduction

The nucleolus is a dynamic non-membrane-bound nuclear organelle, which plays key roles not only in ribosome biogenesis but also in many other cellular processes. Consistent with its multiple functions, the nucleolus has been implicated in many human diseases, including cancer and degenerative pathologies of the nervous system and heart. Here, we report the characterization of the Drosophila Non3 (Novel nucleolar protein 3) gene, which encodes a protein homologous to the human Brix domain-containing Rpf2 that has been shown to control ribosomal RNA (rRNA) processing. We used imprecise P-element excision to generate four new mutant alleles in the Non3 gene. Complementation and phenotypic analyses showed that these Non3 mutations can be arranged in an allelic series that includes both viable and lethal alleles. The strongest lethal allele (Non3∆600) is a genetically null allele that carries a large deletion of the gene and exhibits early lethality when homozygous. Flies heterozygous for Non3∆600 occasionally exhibit a mild reduction in the bristle size, but develop normally and are fertile. However, heteroallelic combinations of viable Non3 mutations (Non3197, Non3310 and Non3259) display a Minute-like phenotype, consisting in delayed development and short and thin bristles, suggesting that they are defective in ribosome biogenesis. We also demonstrate that the Non3 protein localizes to the nucleolus of larval brain cells and it is required for proper nucleolar localization of Fibrillarin, a protein important for post-translational modification and processing of rRNAs. In summary, we generated a number of genetic and biochemical tools that were exploited for an initial characterization of Non3, and will be instrumental for future functional studies on this gene and its protein product.

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