scholarly journals iDPGK: Characterization and Identification of Lysine Phosphoglycerylation Sites Based on Sequence-Based Features

2020 ◽  
Author(s):  
Kai-Yao Huang ◽  
Fang-Yu Hung ◽  
Hui-Ju Kao ◽  
Hui-Hsuan Lau ◽  
Shun-Long Weng
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Training Dataset ◽  
Post Translational Modification ◽  
Web Based ◽  
Charged Amino Acids ◽  
Pair Composition ◽  
Weighted Matrix ◽  
Svm Model ◽  
Effective Performance

Abstract Background:Protein phosphoglycerylation, the addition of a 1,3-bisphosphoglyceric acid (1,3-BPG) to a lysine residue of a protein and thus to form a 3-phosphoglyceryl-lysine (pgK), is a reversible and non-enzymatic post-translational modification (PTM) and plays a regulatory role in glucose metabolism and glycolytic process. As the number of experimentally verified phosphoglycerylated sites has increased significantly, statistical or machine learning methods are imperative for investigating the characteristics of phosphoglycerylation sites. Currently, research into phosphoglycerylation is very limited, and only a few resources are available for the computational identification of phosphoglycerylation sites. Result: We present a bioinformatics investigation of phosphoglycerylation sites based on sequence-based features. The TwoSampleLogo analysis reveals that the regions surrounding the phosphoglycerylation sites contain a high relatively of positively charged amino acids, especially in the upstream flanking region. Additionally, the non-polar and aliphatic amino acids are more abundant surrounding phosphoglycerylated lysine following the results of PTM-Logo, which may play a functional role in discriminating between phosphoglycerylation and non- phosphoglycerylation sites. Many types of features were adopted to build the prediction model on the training dataset, including amino acid composition, amino acid pair composition, positional weighted matrix and position-specific scoring matrix. Further, to improve the predictive power, numerous top features ranked by F-score were considered as the final combination for classification, and thus the predictive models were trained using DT, RF and SVM classifiers. Evaluation by five-fold cross-validation showed that the selected features was most effective in discriminating between phosphoglycerylated and non- phosphoglycerylated sites.Conclusion: The SVM model trained with the selected sequence-based features performed well, with a sensitivity of 77.5%, a specificity of 73.6%, an accuracy of 74.9%, and a Matthews Correlation Coefficient value of 0.49. Furthermore, the model also consistently provides the effective performance in independent testing set, yielding sensitivity of 75.7% and specificity of 64.9%. Finally, the model has been implemented as a web-based system, namely iDPGK, which is now freely available at http://mer.hc.mmh.org.tw/iDPGK/.

scholarly journals iDPGK: characterization and identification of lysine phosphoglycerylation sites based on sequence-based features

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kai-Yao Huang ◽  
Fang-Yu Hung ◽  
Hui-Ju Kao ◽  
Hui-Hsuan Lau ◽  
Shun-Long Weng
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Training Dataset ◽  
Post Translational Modification ◽  
Web Based ◽  
Charged Amino Acids ◽  
Pair Composition ◽  
Weighted Matrix ◽  
Svm Model ◽  
Effective Performance

Abstract Background Protein phosphoglycerylation, the addition of a 1,3-bisphosphoglyceric acid (1,3-BPG) to a lysine residue of a protein and thus to form a 3-phosphoglyceryl-lysine, is a reversible and non-enzymatic post-translational modification (PTM) and plays a regulatory role in glucose metabolism and glycolytic process. As the number of experimentally verified phosphoglycerylated sites has increased significantly, statistical or machine learning methods are imperative for investigating the characteristics of phosphoglycerylation sites. Currently, research into phosphoglycerylation is very limited, and only a few resources are available for the computational identification of phosphoglycerylation sites. Result We present a bioinformatics investigation of phosphoglycerylation sites based on sequence-based features. The TwoSampleLogo analysis reveals that the regions surrounding the phosphoglycerylation sites contain a high relatively of positively charged amino acids, especially in the upstream flanking region. Additionally, the non-polar and aliphatic amino acids are more abundant surrounding phosphoglycerylated lysine following the results of PTM-Logo, which may play a functional role in discriminating between phosphoglycerylation and non-phosphoglycerylation sites. Many types of features were adopted to build the prediction model on the training dataset, including amino acid composition, amino acid pair composition, positional weighted matrix and position-specific scoring matrix. Further, to improve the predictive power, numerous top features ranked by F-score were considered as the final combination for classification, and thus the predictive models were trained using DT, RF and SVM classifiers. Evaluation by five-fold cross-validation showed that the selected features was most effective in discriminating between phosphoglycerylated and non-phosphoglycerylated sites. Conclusion The SVM model trained with the selected sequence-based features performed well, with a sensitivity of 77.5%, a specificity of 73.6%, an accuracy of 74.9%, and a Matthews Correlation Coefficient value of 0.49. Furthermore, the model also consistently provides the effective performance in independent testing set, yielding sensitivity of 75.7% and specificity of 64.9%. Finally, the model has been implemented as a web-based system, namely iDPGK, which is now freely available at http://mer.hc.mmh.org.tw/iDPGK/.

scholarly journals Charged Amino Acids Conserved in the Aromatic Acid/H+ Symporter Family of Permeases Are Required for 4-Hydroxybenzoate Transport by PcaK from Pseudomonas putida

2002 ◽  
Vol 184 (5) ◽  
pp. 1444-1448 ◽  
Author(s):  
Jayna L. Ditty ◽  
Caroline S. Harwood
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Pseudomonas Putida ◽  
Essential Amino Acid ◽  
Major Facilitator Superfamily ◽  
Aromatic Acid ◽  
Transmembrane Segment ◽  
Amino Acid Motif ◽  
Charged Amino Acids ◽  
Major Facilitator

ABSTRACT Charged amino acids in the predicted transmembrane portion of PcaK, a permease from Pseudomonas putida that transports 4-hydroxybenzoate (4-HBA), were required for 4-HBA transport, and they were also required for P. putida to have a chemotactic response to 4-HBA. An essential amino acid motif (DGXD) containing aspartate residues is located in the first transmembrane segment of PcaK and is conserved in the aromatic acid/H+ symporter family of the major facilitator superfamily of transporters.

scholarly journals Negatively charged amino acids in the stalk region of membrane proteins reduce ectodomain shedding

2020 ◽  
Vol 295 (35) ◽  
pp. 12343-12352 ◽  
Author(s):  
Ryo Iwagishi ◽  
Rika Tanaka ◽  
Munenosuke Seto ◽  
Tomoyo Takagi ◽  
Naoko Norioka ◽  
...  
Keyword(s):  
Amino Acids ◽  
Membrane Proteins ◽  
Molecular Mechanisms ◽  
Alternative Exon ◽  
Ectodomain Shedding ◽  
Post Translational Modification ◽  
Charged Amino Acids ◽  
Juxtamembrane Region ◽  
Protein Variants ◽  
Variant Protein

Ectodomain shedding is a post-translational modification mechanism by which the entire extracellular domain of membrane proteins is liberated through juxtamembrane processing. Because shedding rapidly and irreversibly alters the characteristics of cells, this process is properly regulated. However, the molecular mechanisms governing the propensity of membrane proteins to shedding are largely unknown. Here, we present evidence that negatively charged amino acids within the stalk region, an unstructured juxtamembrane region at which shedding occurs, contribute to shedding susceptibility. We show that two activated leukocyte cell adhesion molecule (ALCAM) protein variants produced by alternative splicing have different susceptibilities to ADAM metallopeptidase domain 17 (ADAM17)-mediated shedding. Of note, the inclusion of a stalk region encoded by a 39-bp-long alternative exon conferred shedding resistance. We found that this alternative exon encodes a large proportion of negatively charged amino acids, which we demonstrate are indispensable for conferring the shedding resistance. We also show that the introduction of negatively charged amino acids into the stalk region of shedding-susceptible ALCAM variant protein attenuates its shedding. Furthermore, we observed that negatively charged amino acids residing in the stalk region of Erb-B2 receptor tyrosine kinase 4 (ERBB4) are indispensable for its shedding resistance. Collectively, our results indicate that negatively charged amino acids within the stalk region interfere with the shedding of multiple membrane proteins. We conclude that the composition of the stalk region determines the shedding susceptibility of membrane proteins.

Evaluation of Deformation Mechanisms at Mineral-Protein Composite Interface Using Steered Molecular Dynamics Simulations

2004 ◽  
Vol 844 ◽  
Author(s):  
Dinesh R. Katti ◽  
Pijush Ghosh ◽  
Kalpana Katti
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Amino Acid ◽  
Steered Molecular Dynamics ◽  
Clay Nanocomposites ◽  
Strain Behavior ◽  
New Class ◽  
Charged Amino Acids ◽  
Tension And Compression ◽  
Dynamics Simulations

AbstractIn the area of clay-polymer nanocomposites, recently montmorillonite is extensively used because of its unique characteristics of swelling. In this work, steered molecular dynamics is used to evaluate the mechanical behavior of a new class of nanocomposites, using amino acids to intercalate clay interlayers. Two positively charged amino acids, lysine and arginine, are used here. Our simulation indicates that both the amino acids have preferred orientation inside the clay interlayer. Our simulations also indicate that the clay-amino acid interlayer is about three times stiffer under tension as compared to under compression. On the other hand, dry montmorillonite shows similar stiffness under tension and compression. The fundamental mechanism of deformation during tension and compression is intrinsically different in the amino acid-clay composite. The stress-strain behavior of this clay-amino acid interlayer is predominantly linear until a stress of 1.5 GPa. This study is a first step towards the potential use of biomacromolecules as modifiers in clay nanocomposites.

scholarly journals The Use of GC-, Codon-, and Amino Acid-frequencies to Understand the Evolutionary Forces at a Genomic Scale

2019 ◽  
Author(s):  
Arne Elofsson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Selective Pressure ◽  
Amino Acid Level ◽  
Gc Content ◽  
Frequency Variation ◽  
Evolutionary Forces ◽  
Charged Amino Acids ◽  
Plausible Model ◽  
Selective Forces

1AbstractIt is well known that the GC content varies enormously between organisms; this is believed to be caused by a combination of mutational preferences and selective pressure. Within coding regions, the variation of GC is more substantial in position three and smaller in position one and two. Less well known is that this variation also has an enormous impact on the frequency of amino acids as their codons vary in GC content. For instance, the fraction of alanines in different proteomes varies from 1.1% to 16.5%. In general, the frequency of different amino acids correlates strongly with the number of codons, the GC content of these codons and the genomic GC contents. However, there are clear and systematic deviations from the expected frequencies. Some amino acids are more frequent than expected by chance, while others are less frequent. A plausible model to explain this is that there exist two different selective forces acting on the genes; First, there exists a force acting to maintain the overall GC level and secondly there exists a selective force acting on the amino acid level. Here, we use the divergence in amino acid frequency from what is expected by the GC content to analyze the selective pressure acting on codon frequencies in the three kingdoms of life. We find four major selective forces; First, the frequency of serine is lower than expected in all genomes, but most in prokaryotes. Secondly, there exist a selective pressure acting to balance positively and negatively charged amino acids, which results in a reduction of arginine and negatively charged amino acids. This results in a reduction of arginine and all the negatively charged amino acids. Thirdly, the frequency of the hydrophobic residues encoded by a T in the second codon position does not change with GC. Their frequency is lower in eukaryotes than in prokaryotes. Finally, some amino acids with unique properties, such as proline glycine and proline, are limited in their frequency variation.

scholarly journals The bioactivity of soluble Fas ligand is modulated by key amino acids of its stalk region

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253260
Author(s):  
Osamu Kajikawa ◽  
Raquel Herrero ◽  
Yu-Hua Chow ◽  
Chi F. Hung ◽  
Gustavo Matute-Bello
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
T Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Fas Ligand ◽  
Wild Type ◽  
Soluble Fas ◽  
Charged Amino Acids ◽  
Soluble Fas Ligand

We have previously reported that the 26-amino acid N-terminus stalk region of soluble Fas ligand (sFasL), which is separate from its binding site, is required for its biological function. Here we investigate the mechanisms that link the structure of the sFasL stalk region with its function. Using site-directed mutagenesis we cloned a mutant form of sFasL in which all the charged amino acids of the stalk region were changed to neutral alanines (mut-sFasL). We used the Fas-sensitive Jurkat T-cell line and mouse and human alveolar epithelial cells to test the bioactivity of sFasL complexes, using caspase-3 activity and Annexin-V externalization as readouts. Finally, we tested the effects of mut-sFasL on lipopolysaccharide-induced lung injury in mice. We found that mutation of all the 8 charged amino acids of the stalk region into the non-charged amino acid alanine (mut-sFasL) resulted in reduced apoptotic activity compared to wild type sFasL (WT-sFasL). The mut-sFasL attenuated WT-sFasL function on the Fas-sensitive human T-cell line Jurkat and on primary human small airway epithelial cells. The inhibitory mechanism was associated with the formation of complexes of mut-sFasL with the WT protein. Intratracheal administration of the mut-sFasL to mice 24 hours after intratracheal Escherichia coli lipopolysaccharide resulted in attenuation of the inflammatory response 24 hours later. Therefore, the stalk region of sFasL has a critical role on bioactivity, and changes in the structure of the stalk region can result in mutant variants that interfere with the wild type protein function in vitro and in vivo.

Tetraphenyl porphyrin films as selective detectors for amino acid molecules

2020 ◽  
Vol 24 (10) ◽  
pp. 1215-1223
Author(s):  
Jesús Miguel Rivera ◽  
Margarita Rivera
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Quartz Crystal Microbalance ◽  
Quartz Crystal ◽  
Binding Energies ◽  
Charged Amino Acids ◽  
Tetraphenyl Porphyrin ◽  
Pseudo Second Order ◽  
Selective Detectors ◽  
Positively Charged

The interaction of different amino acids and vacuum evaporated tetraphenyl porphyrin films was investigated by using kinetic isotherms, UV-vis spectroscopy, quartz crystal microbalance and density functional theory techniques. The adsorption process was analyzed by using pseudo-first-order and pseudo-second-order models. From these results, the adsorption order changed depending on the chemical characteristics of the porphyrin film, although most of the interactions were classified as pseudo-second-order at the films interface. From absorbance measurements, red shifts on the Soret peak positions were observed for all amino acids interacting with the metal free and the ZnTPP systems, while the position of the Soret peak barely change for the CuTPP surface, except for a slight bathocromic shift for arginine. On the other hand, the broadening of the Soret peak was more important for the ZnTPP and H2TPP surfaces, but the interaction with the CuTPP interfaces decreased the width of the peaks in all cases. In addition, a quartz crystal microbalance analysis was employed to investigate the film sensing performance during amino acid exposure. From these results, positively charged amino acids were more easily adsorbed on the films in contrast with the polar (serine) molecule. DFT calculations exhibited important deformations for H2TPP, the out-of-plane displacement of the Zn atom for ZnTPP, and hydrogen bond interactions with the CuTPP molecule. DFT also showed high binding energies for the positively charged amino acids but low binding energies for serine in agreement with experimental data. From these results, porphyrin films could be used as selective detectors for various L-amino acid molecules.

scholarly journals Structure-Activity Relationship of Synthetic Variants of the Milk-Derived Antimicrobial Peptide αs2-Casein f(183–207)

2013 ◽  
Vol 79 (17) ◽  
pp. 5179-5185 ◽  
Author(s):  
Avelino Alvarez-Ordóñez ◽  
Máire Begley ◽  
Tanya Clifford ◽  
Thérèse Deasy ◽  
Kiera Considine ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Amino Acid ◽  
Antimicrobial Peptide ◽  
Peptide Sequence ◽  
Content Type ◽  
Charged Amino Acids ◽  
Food Borne ◽  
Relationship Of ◽  
Positively Charged

ABSTRACTTemplate-based studies on antimicrobial peptide (AMP) derivatives obtained through manipulation of the amino acid sequence are helpful to identify properties or residues that are important for biological activity. The present study sheds light on the importance of specific amino acids of the milk-derived αs2-casein f(183–207) peptide to its antibacterial activity against the food-borne pathogensListeria monocytogenesandCronobacter sakazakii. Trimming of the peptide revealed that residues at the C-terminal end of the peptide are important for activity. Removal of the last 5 amino acids at the C-terminal end and replacement of the Arg at position 23 of the peptide sequence by an Ala residue significantly decreased activity. These findings suggest that Arg23 is very important for optimal activity of the peptide. Substitution of the also positively charged Lys residues at positions 15 and 17 of the αs2-casein f(183–207) peptide also caused a significant reduction of the effectiveness againstC. sakazakii, which points toward the importance of the positive charge of the peptide for its biological activity. Indeed, simultaneous replacement of various positively charged amino acids was linked to a loss of bactericidal activity. On the other hand, replacement of Pro residues at positions 14 and 20 resulted in a significantly increased antibacterial potency, and hydrophobic end tagging of αs2-casein f(193–203) and αs2-casein f(197–207) peptides with multiple Trp or Phe residues significantly increased their potency againstL. monocytogenes. Finally, the effect of pH (4.5 to 7.4), temperature (4°C to 37°C), and addition of sodium and calcium salts (1% to 3%) on the activity of the 15-amino-acid αs2-casein f(193–207) peptide was also determined, and its biological activity was shown to be completely abolished in high-saline environments.

scholarly journals Amino Acid Contacts between Sigma 70 Domain 4 and the Transcription Activators RhaS and RhaR

2004 ◽  
Vol 186 (18) ◽  
pp. 6277-6285 ◽  
Author(s):  
Jason R. Wickstrum ◽  
Susan M. Egan
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Level ◽  
Transcription Activation ◽  
Charged Amino Acids ◽  
Specific Contact ◽  
Loss Of Contact ◽  
Transcription Activators ◽  
Sigma 70 ◽  
Positively Charged

ABSTRACT The RhaS and RhaR proteins are transcription activators that respond to the availability of l-rhamnose and activate transcription of the operons in the Escherichia coli l-rhamnose catabolic regulon. RhaR activates transcription of rhaSR, and RhaS activates transcription of the operon that encodes the l-rhamnose catabolic enzymes, rhaBAD, as well as the operon that encodes the l-rhamnose transport protein, rhaT. RhaS is 30% identical to RhaR at the amino acid level, and both are members of the AraC/XylS family of transcription activators. The RhaS and RhaR binding sites overlap the −35 hexamers of the promoters they regulate, suggesting they may contact the σ70 subunit of RNA polymerase as part of their mechanisms of transcription activation. In support of this hypothesis, our lab previously identified an interaction between RhaS residue D241 and σ70 residue R599. In the present study, we first identified two positively charged amino acids in σ70, K593 and R599, and three negatively charged amino acids in RhaR, D276, E284, and D285, that were important for RhaR-mediated transcription activation of the rhaSR operon. Using a genetic loss-of-contact approach we have obtained evidence for a specific contact between RhaR D276 and σ70 R599. Finally, previous results from our lab separately showed that RhaS D250A and σ70 K593A were defective at the rhaBAD promoter. Our genetic loss-of-contact analysis of these residues indicates that they identify a second site of contact between RhaS and σ70.

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