scholarly journals Biochemical Characterization of Arylamine N-acetyltransferases From Vibrio vulnificus

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinning Liu ◽  
Yuanchang Liu ◽  
Guangjian Zhao ◽  
Yidan Zhang ◽  
Lu Liu ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Aromatic Amine ◽  
Biochemical Characterization ◽  
Vibrio Vulnificus ◽  
Docking Study ◽  
The United States ◽  
Molecular Docking Study ◽  
Different Temperatures ◽  
Amino Salicylic Acid ◽  
High Concentrations

Vibrio vulnificus is a zoonotic bacterium that is capable of causing highly lethal diseases in humans; this pathogen is responsible for 95% of all seafood-related deaths in the United States. Arylamine N-acetyltransferases (NAT, E.C. 2.3.1.5) is a major family of xenobiotic-metabolizing enzymes that can biotransform aromatic amine chemicals. In this research, to evaluate the effect of NAT on acetyl group transformation in arylamine antibiotics, we first used sequence alignment to study the structure of V. vulnificus NAT [(VIBVN)NAT]. The nat gene encodes a protein of 260 amino acids, which has an approximate molecular mass of 30 kDa. Then we purified recombinant (VIBVN)NAT and determined the enzyme activity by PNPA and DTNB methods. The DTNB method indicates that this prokaryotic NAT has a particular substrate specificity towards aromatic substrates. However, (VIBVN)NAT lost most of its activity after treatment with high concentrations of urea and H2O2. In addition, we also explored the stability of the enzyme at different temperatures and pH values. In analyzing the influence of metal ions, the enzyme activity was significantly inhibited by Zn2+ and Cu2+. The kinetic parameters Km and Vmax were determined using hydralazine, isoniazid, 4-amino salicylic acid, and 4-chloro-3-methylaniline as substrates, and the Tm, Tagg and size distribution of (VIBVN)NAT were observed. In particular, a molecular docking study on the structure of (VIBVN)NAT was conducted to understand its biochemical traits. These results showed that (VIBVN)NAT could acetylate various aromatic amine substrates and contribute to arylamine antibiotic resistance in V. vulnificus.

Potential angiotensin I converting enzyme inhibitory peptides from gluten hydrolysate: Biochemical characterization and molecular docking study

2014 ◽  
Vol 60 (1) ◽  
pp. 92-98 ◽  
Author(s):  
Ahmad Asoodeh ◽  
Leyla Haghighi ◽  
Jamashidkhan Chamani ◽  
Mohamad Amin Ansari-Ogholbeyk ◽  
Zahra Mojallal-Tabatabaei ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biochemical Characterization ◽  
Docking Study ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Molecular Docking Study ◽  
Inhibitory Peptides ◽  
Angiotensin I Converting Enzyme

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Myricetin Preferentially Binds to Interfacial Regions in Domains 1 – 3 to Inhibit Cholesterol-Dependent Cytolysins: A Molecular Docking Study

2020 ◽  
Author(s):  
Rafael Espiritu
Keyword(s):  
Molecular Docking ◽  
Structural Changes ◽  
Docking Study ◽  
Listeriolysin O ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Streptolysin O ◽  
Molecule Inhibitor ◽  
Human Cd59 ◽  
Anthrolysin O

<p>Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was common among the tested CDCs, which was primarily due to much more extensive stabilizing intermolecular interactions, as indicated by post-docking analysis. Specifically, myricetin bound to (1) the interface of the three domains in anthrolysin O (ALO), perfringolysin O (PFO), pneumolysin (PLY), SLY, and vaginolysin (VLY), (2) at/near the D1/D3 interface in LLO and streptolysin O (SLO), and (3) along the D2/D3 interface in intermedilysin (ILY). These findings provide theoretical basis on the possibility of using myricetin and its related compounds as a broad-spectrum inhibitor of CDCs to potentially address the diseases associated with these pathogens.</p>

Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach Against COVID-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Rashmi Mittal ◽  
Vedpriya Arya
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Bond Distance ◽  
Immunological Response ◽  
Docking Study ◽  
Receptor Interaction ◽  
Molecular Docking Study ◽  
Replication Process ◽  
Stable Conformation ◽  
Distance Analysis

Background:: COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered as potential drug target to combat the current pandemic. Methods:: Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore, average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed to predict the strength of interaction. Results:: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study. RMSD average values were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET exploration further validated the drug like properties of these compounds. Conclusion:: Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially used to target SARS-CoV-2 by hindering its replication process.

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