Role of Peptide Sequence and Neighboring Residue Glycosylation on the Substrate Specificity of the Uridine 5'-Diphosphate−α-N-acetylgalactosamine:PolypeptideN-acetylgalactosaminyl Transferases T1 and T2:  Kinetic Modeling of the Porcine and Canine Submaxillary Gland Mucin Tandem Repeats†

Biochemistry ◽  
2004 ◽  
Vol 43 (30) ◽  
pp. 9888-9900 ◽  
Author(s):  
Thomas A. Gerken ◽  
Chhavy Tep ◽  
Jason Rarick
Keyword(s):  
Substrate Specificity ◽  
Kinetic Modeling ◽  
Tandem Repeats ◽  
Submaxillary Gland ◽  
Peptide Sequence ◽  
T1 And T2 ◽  
Neighboring Residue

scholarly journals Involvement of Very Short DNA Tandem Repeats and the Influence of the RAD52 Gene on the Occurrence of Deletions in Saccharomyces cerevisiae

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 549-557 ◽  
Author(s):  
Anne J Welcker ◽  
Jacky de Montigny ◽  
Serge Potier ◽  
Jean-Luc Souciet
Keyword(s):  
Fusion Proteins ◽  
Tandem Repeats ◽  
Chromosomal Rearrangements ◽  
Reversion Rate ◽  
Wild Type ◽  
Recombination Mechanism ◽  
Nonhomologous Recombination ◽  
Deletion Rate ◽  
Dna Tandem Repeats

Abstract Chromosomal rearrangements, such as deletions, duplications, or Ty transposition, are rare events. We devised a method to select for such events as Ura+ revertants of a particular ura2 mutant. Among 133 Ura+ revertants, 14 were identified as the result of a deletion in URA2. Of seven classes of deletions, six had very short regions of identity at their junctions (from 7 to 13 bp long). This strongly suggests a nonhomologous recombination mechanism for the formation of these deletions. The total Ura+ reversion rate was increased 4.2-fold in a rad52Δ strain compared to the wild type, and the deletion rate was significantly increased. All the deletions selected in the rad52Δ context had microhomologies at their junctions. We propose two mechanisms to explain the occurrence of these deletions and discuss the role of microhomology stretches in the formation of fusion proteins.

scholarly journals Arsenic Removal by Advanced Electrocoagulation Processes: The Role of Oxidants Generated and Kinetic Modeling

Catalysts ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 928
Author(s):  
Micah Flor V. Montefalcon ◽  
Meliton R. Chiong ◽  
Augustus C. Resurreccion ◽  
Sergi Garcia-Segura ◽  
Joey D. Ocon
Keyword(s):  
Kinetic Modeling ◽  
Arsenic Removal ◽  
Fold Increase ◽  
Electrochemical Treatment ◽  
Promising Alternative ◽  
Iron Electrodes ◽  
Removal Capacity ◽  
Naturally Occurring ◽  
Treatment Technologies

Arsenic (As) is a naturally occurring element in the environment that poses significant risks to human health. Several treatment technologies have been successfully used in the treatment of As-contaminated waters. However, limited literature has explored advanced electrocoagulation (EC) processes for As removal. The present study evaluates the As removal performance of electrocoagulation, electrochemical peroxidation (ECP), and photo-assisted electrochemical peroxidation (PECP) technologies at circumneutral pH using electroactive iron electrodes. The influence of As speciation and the role of oxidants in As removal were investigated. We have identified the ECP process to be a promising alternative for the conventional EC with around 4-fold increase in arsenic removal capacity at a competitive cost of 0.0060 $/m3. Results also indicated that the rate of As(III) oxidation at the outset of electrochemical treatment dictates the extent of As removal. Both ECP and PECP processes reached greater than 96% As(III) conversion at 1 C/L and achieved 86% and 96% As removal at 5 C/L, respectively. Finally, the mechanism of As(III) oxidation was evaluated, and results showed that Fe(IV) is the intermediate oxidant generated in advanced EC processes, and the contribution of •OH brought by UV irradiation is insignificant.

scholarly journals A Novel Tetrapeptide Derivative Exhibits In Vitro Inhibition of Neutrophil-Derived Reactive Oxygen Species and Lysosomal Enzymes Release

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
Meera Ramanujam ◽  
Rengarajulu Puvanakrishnan
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Anion ◽  
Lysosomal Enzymes ◽  
Reactive Oxygen ◽  
Peptide Sequence ◽  
Ros Generation ◽  
Oxygen Species ◽  
Complement Factors

Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39–42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.

Possible role of a histidine residue in the substrate specificity of yeast d-aspartate oxidase

2015 ◽  
pp. mvv108 ◽  
Author(s):  
Shouji Takahashi ◽  
Kozue Shimada ◽  
Shunsuke Nozawa ◽  
Masaru Goto ◽  
Katsumasa Abe ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Histidine Residue

HemoNet: Predicting hemolytic activity of peptides with integrated feature learning

2021 ◽  
pp. 2150021
Author(s):  
Adiba Yaseen ◽  
Sadaf Gull ◽  
Naeem Akhtar ◽  
Imran Amin ◽  
Fayyaz Minhas
Keyword(s):  
Amino Acids ◽  
Hemolytic Activity ◽  
Cross Validation ◽  
Feature Learning ◽  
Predictive Performance ◽  
Peptide Sequence ◽  
Therapeutic Peptides ◽  
Wet Lab ◽  
Novel Therapeutic

Quantifying the hemolytic activity of peptides is a crucial step in the discovery of novel therapeutic peptides. Computational methods are attractive in this domain due to their ability to guide wet-lab experimental discovery or screening of peptides based on their hemolytic activity. However, existing methods are unable to accurately model various important aspects of this predictive problem such as the role of N/C-terminal modifications, D- and L- amino acids, etc. In this work, we have developed a novel neural network-based approach called HemoNet for predicting the hemolytic activity of peptides. The proposed method captures the contextual importance of different amino acids in a given peptide sequence using a specialized feature embedding in conjunction with SMILES-based fingerprint representation of N/C-terminal modifications. We have analyzed the predictive performance of the proposed method using stratified cross-validation in comparison with previous methods, non-redundant cross-validation as well as validation on external peptides and clinical antimicrobial peptides. Our analysis shows the proposed approach achieves significantly better predictive performance (AUC-ROC of 88%) in comparison to previous approaches (HemoPI and HemoPred with AUC-ROC of 73%). HemoNet can be a useful tool in the search for novel therapeutic peptides. The python implementation of the proposed method is available at the URL: https://github.com/adibayaseen/HemoNet.

scholarly journals Molecular Basis of Substrate Recognition of Endonuclease Q from the Euryarchaeon Pyrococcus furiosus

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Miyako Shiraishi ◽  
Shigenori Iwai
Keyword(s):  
Dna Repair ◽  
Bacillus Subtilis ◽  
Substrate Specificity ◽  
Molecular Basis ◽  
Pyrococcus Furiosus ◽  
Substrate Recognition ◽  
Base Flipping ◽  
Content Type ◽  
Cleavage Activity

ABSTRACT Endonuclease Q (EndoQ), a DNA repair endonuclease, was originally identified in the hyperthermophilic euryarchaeon Pyrococcus furiosus in 2015. EndoQ initiates DNA repair by generating a nick on DNA strands containing deaminated bases and an abasic site. Although EndoQ is thought to be important for maintaining genome integrity in certain bacteria and archaea, the underlying mechanism catalyzed by EndoQ remains unclear. Here, we provide insights into the molecular basis of substrate recognition by EndoQ from P. furiosus (PfuEndoQ) using biochemical approaches. Our results of the substrate specificity range and the kinetic properties of PfuEndoQ demonstrate that PfuEndoQ prefers the imide structure in nucleobases along with the discovery of its cleavage activity toward 5,6-dihydrouracil, 5-hydroxyuracil, 5-hydroxycytosine, and uridine in DNA. The combined results for EndoQ substrate binding and cleavage activity analyses indicated that PfuEndoQ flips the target base from the DNA duplex, and the cleavage activity is highly dependent on spontaneous base flipping of the target base. Furthermore, we find that PfuEndoQ has a relatively relaxed substrate specificity; therefore, the role of EndoQ in restriction modification systems was explored. The activity of the EndoQ homolog from Bacillus subtilis was found not to be inhibited by the uracil glycosylase inhibitor from B. subtilis bacteriophage PBS1, whose genome is completely replaced by uracil instead of thymine. Our findings suggest that EndoQ not only has additional functions in DNA repair but also could act as an antiviral enzyme in organisms with EndoQ. IMPORTANCE Endonuclease Q (EndoQ) is a lesion-specific DNA repair enzyme present in certain bacteria and archaea. To date, it remains unclear how EndoQ recognizes damaged bases. Understanding the mechanism of substrate recognition by EndoQ is important to grasp genome maintenance systems in organisms with EndoQ. Here, we find that EndoQ from the euryarchaeon Pyrococcus furiosus recognizes the imide structure in nucleobases by base flipping, and the cleavage activity is enhanced by the base pair instability of the target base, along with the discovery of its cleavage activity toward 5,6-dihydrouracil, 5-hydroxyuracil, 5-hydroxycytosine, and uridine in DNA. Furthermore, a potential role of EndoQ in Bacillus subtilis as an antiviral enzyme by digesting viral genome is demonstrated.

The Role of the 5'-Hydroxyl Group of Adenosine in Determining Substrate Specificity for Adenosine Deaminase

1967 ◽  
Vol 10 (5) ◽  
pp. 908-912 ◽  
Author(s):  
Alexander. Bloch ◽  
Morris J. Robins ◽  
James R. McCarthy
Keyword(s):  
Substrate Specificity ◽  
Adenosine Deaminase ◽  
Hydroxyl Group

scholarly journals The role of the Cys191-Cys220 disulfide bond in trypsin: new targets for engineering substrate specificity

1997 ◽  
Vol 10 (4) ◽  
pp. 405-411 ◽  
Author(s):  
E. C. Wang ◽  
S. H. Hung ◽  
M. Cahoon ◽  
L. Hedstrom
Keyword(s):  
Substrate Specificity ◽  
Disulfide Bond ◽  
New Targets

Bimodal evolution of Src and Abl kinase substrate specificity revealed using mammalian cell extract as substrate pool

2020 ◽  
Author(s):  
Patrick Finneran ◽  
Margaret Soucheray ◽  
Christopher Wilson ◽  
Renee Otten ◽  
Vanessa Buosi ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Mammalian Cell ◽  
Tyrosine Kinases ◽  
Cell Extract ◽  
Peptide Sequence ◽  
Last Common Ancestor ◽  
Sequence Specificity ◽  
Kinase Substrate ◽  
Evolutionary Trajectories ◽  
Substrate Proteins

AbstractThe specificity of phosphorylation by protein kinases is essential to the integrity of biological signal transduction. While peptide sequence specificity for individual kinases has been examined previously, here we explore the evolutionary progression that has led to the modern substrate specificity of two non-receptor tyrosine kinases, Abl and Src. To efficiently determine the substrate specificity of modern and reconstructed ancestral kinases, we developed a method using mammalian cell lysate as the substrate pool, thereby representing the naturally occurring substrate proteins. We find that the oldest tyrosine kinase ancestor was a promiscuous enzyme that evolved through a more specific last common ancestor into a specific human Abl. In contrast, the parallel pathway to human Src involved a loss of substrate specificity, leading to general promiscuity. These results add a new facet to our understanding of the evolution of signaling pathways, with both subfunctionalization and neofunctionalization along the evolutionary trajectories.

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