scholarly journals Hyperoxidation of Peroxiredoxin 6 Induces Alteration from Dimeric to Oligomeric State

Antioxidants ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 33 ◽  
Author(s):  
Sharifun Shahnaj ◽  
Rimpy Chowhan ◽  
Potshangbam Meetei ◽  
Pushpa Kakchingtabam ◽  
Khundrakpam Herojit Singh ◽  
...  
Keyword(s):  
Root Mean Square ◽  
Mean Square ◽  
Hydrophobic Core ◽  
Post Translational Modification ◽  
Oligomeric State ◽  
Native Page ◽  
Peroxiredoxin 6 ◽  
Glutathione Peroxidases ◽  
Mean Square Fluctuation ◽  
Calcium Independent Phospholipase A2

Peroxiredoxins(Prdx), the family of non-selenium glutathione peroxidases, are important antioxidant enzymes that defend our system from the toxic reactive oxygen species (ROS). They are thiol-based peroxidases that utilize self-oxidation of their peroxidatic cysteine (Cp) group to reduce peroxides and peroxidized biomolecules. However, because of its high affinity for hydrogen peroxide this peroxidatic cysteine moiety is extremely susceptible to hyperoxidation, forming peroxidase inactive sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) derivatives. With the exception of peroxiredoxin 6 (Prdx6), hyperoxidized sulfinic forms of Prdx can be reversed to restore peroxidase activity by the ATP-dependent enzyme sulfiredoxin. Interestingly, hyperoxidized Prdx6 protein seems to have physiological significance as hyperoxidation has been reported to dramatically upregulate its calcium independent phospholipase A2 activity. Using biochemical studies and molecular dynamic (MD) simulation, we investigated the roles of thermodynamic, structural and internal flexibility of Prdx6 to comprehend the structural alteration of the protein in the oxidized state. We observed the loosening of the hydrophobic core of the enzyme in its secondary and tertiary structures. These changes do not affect the internal dynamics of the protein (as indicated by root-mean-square deviation, RMSD and root mean square fluctuation, RMSF plots). Native-PAGE and dynamic light scattering experiments revealed the formation of higher oligomers of Prdx6 under hyperoxidation. Our study demonstrates that post translational modification (like hyperoxidation) in Prdx6 can result in major alterations of its multimeric status.

scholarly journals Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 260
Author(s):  
Trina Ekawati Tallei ◽  
Fatimawali ◽  
Ahmad Akroman Adam ◽  
Mona M. Elseehy ◽  
Ahmed M. El-Shehawi ◽  
...  
Keyword(s):  
Root Mean Square ◽  
Antiviral Agents ◽  
Md Simulations ◽  
Radius Of Gyration ◽  
Mean Square ◽  
Angiotensin Converting Enzyme 2 ◽  
In Silico Study ◽  
Mean Square Fluctuation ◽  
Binding Residues ◽  
Binding Energy Calculations

Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.

scholarly journals Engineering the Enantioselectivity and Thermostability of a (+)-γ-Lactamase from Microbacterium hydrocarbonoxydans for Kinetic Resolution of Vince Lactam (2-Azabicyclo[2.2.1]hept-5-en-3-one)

2017 ◽  
Vol 84 (1) ◽  
Author(s):  
Shuaihua Gao ◽  
Shaozhou Zhu ◽  
Rong Huang ◽  
Hongxia Li ◽  
Hao Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Protein Engineering ◽  
Root Mean Square ◽  
Active Site ◽  
Kinetic Resolution ◽  
Mean Square ◽  
Content Type ◽  
Enantiomerically Pure ◽  
Mean Square Fluctuation ◽  
Microbacterium Hydrocarbonoxydans

ABSTRACT To produce promising biocatalysts, natural enzymes often need to be engineered to increase their catalytic performance. In this study, the enantioselectivity and thermostability of a (+)-γ-lactamase from Microbacterium hydrocarbonoxydans as the catalyst in the kinetic resolution of Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) were improved. Enantiomerically pure (−)-Vince lactam is the key synthon in the synthesis of antiviral drugs, such as carbovir and abacavir, which are used to fight against HIV and hepatitis B virus. The work was initialized by using the combinatorial active-site saturation test strategy to engineer the enantioselectivity of the enzyme. The approach resulted in two mutants, Val54Ser and Val54Leu, which catalyzed the hydrolysis of Vince lactam to give (−)-Vince lactam, with 99.2% (enantiomeric ratio [E] > 200) enantiomeric excess (ee) and 99.5% ee (E > 200), respectively. To improve the thermostability of the enzyme, 11 residues with high temperature factors (B-factors) calculated by B-FITTER or high root mean square fluctuation (RMSF) values from the molecular dynamics simulation were selected. Six mutants with increased thermostability were obtained. Finally, the mutants generated with improved enantioselectivity and mutants evolved for enhanced thermostability were combined. Several variants showing (+)-selectivity (E value > 200) and improved thermostability were observed. These engineered enzymes are good candidates to serve as enantioselective catalysts for the preparation of enantiomerically pure Vince lactam. IMPORTANCE Enzymatic kinetic resolution of the racemic Vince lactam using (+)-γ-lactamase is the most often utilized means of resolving the enantiomers for the preparation of carbocyclic nucleoside compounds. The efficiency of the native enzymes could be improved by using protein engineering methods, such as directed evolution and rational design. In our study, two properties (enantioselectivity and thermostability) of a γ-lactamase identified from Microbacterium hydrocarbonoxydans were tackled using a semirational design. The protein engineering was initialized by combinatorial active-site saturation test to improve the enantioselectivity. At the same time, two strategies were applied to identify mutation candidates to enhance the thermostability based on calculations from both a static (B-FITTER based on the crystal structure) and a dynamic (root mean square fluctuation [RMSF] values based on molecular dynamics simulations) way. After combining the mutants, we successfully obtained the final mutants showing better properties in both properties. The engineered (+)-lactamase could be a candidate for the preparation of (−)-Vince lactam.

The Relationship of Root Mean Square Value of Electromyography and Isometric Torque of Quadriceps in Normal Subjects

2016 ◽  
Vol 26 (1) ◽  
pp. 58
Author(s):  
Qiurong XIE ◽  
Zheng JIANG ◽  
Qinglu LUO ◽  
Jie LIANG ◽  
Xiaoling WANG ◽  
...  
Keyword(s):  
Root Mean Square ◽  
Normal Subjects ◽  
Mean Square ◽  
Isometric Torque ◽  
Relationship Of ◽  
The Relationship

scholarly journals Estimation of Apple Flowering Frost Loss for Fruit Yield Based on Gridded Meteorological and Remote Sensing Data in Luochuan, Shaanxi Province, China

2021 ◽  
Vol 13 (9) ◽  
pp. 1630
Author(s):  
Yaohui Zhu ◽  
Guijun Yang ◽  
Hao Yang ◽  
Fa Zhao ◽  
Shaoyu Han ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Root Mean Square Error ◽  
Mean Square Error ◽  
Root Mean Square ◽  
Minimum Temperature ◽  
Price Regulation ◽  
Flowering Period ◽  
Mean Square ◽  
Prevention Measures ◽  
Agricultural Insurance

With the increase in the frequency of extreme weather events in recent years, apple growing areas in the Loess Plateau frequently encounter frost during flowering. Accurately assessing the frost loss in orchards during the flowering period is of great significance for optimizing disaster prevention measures, market apple price regulation, agricultural insurance, and government subsidy programs. The previous research on orchard frost disasters is mainly focused on early risk warning. Therefore, to effectively quantify orchard frost loss, this paper proposes a frost loss assessment model constructed using meteorological and remote sensing information and applies this model to the regional-scale assessment of orchard fruit loss after frost. As an example, this article examines a frost event that occurred during the apple flowering period in Luochuan County, Northwestern China, on 17 April 2020. A multivariable linear regression (MLR) model was constructed based on the orchard planting years, the number of flowering days, and the chill accumulation before frost, as well as the minimum temperature and daily temperature difference on the day of frost. Then, the model simulation accuracy was verified using the leave-one-out cross-validation (LOOCV) method, and the coefficient of determination (R2), the root mean square error (RMSE), and the normalized root mean square error (NRMSE) were 0.69, 18.76%, and 18.76%, respectively. Additionally, the extended Fourier amplitude sensitivity test (EFAST) method was used for the sensitivity analysis of the model parameters. The results show that the simulated apple orchard fruit number reduction ratio is highly sensitive to the minimum temperature on the day of frost, and the chill accumulation and planting years before the frost, with sensitivity values of ≥0.74, ≥0.25, and ≥0.15, respectively. This research can not only assist governments in optimizing traditional orchard frost prevention measures and market price regulation but can also provide a reference for agricultural insurance companies to formulate plans for compensation after frost.

scholarly journals Histamine Control in Raw and Processed Tuna: A Rapid Tool Based on NIR Spectroscopy

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 885
Author(s):  
Sergio Ghidini ◽  
Luca Maria Chiesa ◽  
Sara Panseri ◽  
Maria Olga Varrà ◽  
Adriana Ianieri ◽  
...  
Keyword(s):  
Root Mean Square ◽  
Near Infrared ◽  
Nir Spectroscopy ◽  
Partial Least Square ◽  
Least Square ◽  
Partial Least Square Regression ◽  
Coefficient Of Determination ◽  
Mean Square ◽  
Tuna Fish ◽  
Mean Square Errors

The present study was designed to investigate whether near infrared (NIR) spectroscopy with minimal sample processing could be a suitable technique to rapidly measure histamine levels in raw and processed tuna fish. Calibration models based on orthogonal partial least square regression (OPLSR) were built to predict histamine in the range 10–1000 mg kg−1 using the 1000–2500 nm NIR spectra of artificially-contaminated fish. The two models were then validated using a new set of naturally contaminated samples in which histamine content was determined by conventional high-performance liquid chromatography (HPLC) analysis. As for calibration results, coefficient of determination (r2) > 0.98, root mean square of estimation (RMSEE) ≤ 5 mg kg−1 and root mean square of cross-validation (RMSECV) ≤ 6 mg kg−1 were achieved. Both models were optimal also in the validation stage, showing r2 values > 0.97, root mean square errors of prediction (RMSEP) ≤ 10 mg kg−1 and relative range error (RER) ≥ 25, with better results showed by the model for processed fish. The promising results achieved suggest NIR spectroscopy as an implemental analytical solution in fish industries and markets to effectively determine histamine amounts.

Sign in / Sign up

Export Citation Format

Share Document