scholarly journals DESIGNING OF COUMARIN DERIVATIVES AS SQUALENE SYNTHASE INHIBITORS

2018 ◽  
Vol 11 (10) ◽  
pp. 200 ◽  
Author(s):  
Firoz Mv ◽  
Vishwanathan Balasubramanya Iyer ◽  
Vishal Gupta N ◽  
Gowda Dv ◽  
Gurupadayya Bm ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Research Work ◽  
Three Dimensional ◽  
Data Bank ◽  
Squalene Synthase ◽  
Dimensional Structure ◽  
Binding Property ◽  
Coumarin Derivatives ◽  
Human Squalene Synthase ◽  
Synthase Inhibitor

Objective: The importance of this research work is to design a library of novel coumarin derivatives by docking evaluation of the designed coumarin derivatives as squalene synthase inhibitor.Methods: The three-dimensional structure of designed molecules of squalene synthase inhibitors was collected from Protein Data Bank. The designed molecules were docked onto the enzymes that are squalene synthase inhibitor - 3WCM, 3WCJ, and 3Q2Z protein using SYBYL-X 2.1. Using a standard protocol, the protein was subjected to minimization and protomol generation.Results: By this method, we visualized the possible binding and also estimated the protein interactions with our intended coumarin library, using SYBYL-X 2.1 software. Into the active site of the selected enzymes, all the 20 coumarins were docked and then the docking scores revealed that the compounds possess high affinity toward the selected enzymes.Conclusion: With the help of virtual evaluation, we have elaborated a fast synthetically accessible coumarin-based compounds, and it is an advanced and original scaffold in the area of probable human squalene synthase inhibitors. Some of the developed compounds show better binding property than ligand, and in 3q2Z, the compound 5d shows better binding property than the protein. Furthermore, 6g and 6c have good binding property. In 3 WCM, the compound 6f has better property. In 3 WCJ, the compounds 6g and 6f show better binding property than the protein.

scholarly journals A computer-based approach for developing linamarase inhibitory agents

2020 ◽  
Vol 5 (7) ◽  
Author(s):  
Lucas Paul ◽  
Celestin N. Mudogo ◽  
Kelvin M. Mtei ◽  
Revocatus L. Machunda ◽  
Fidele Ntie-Kang
Keyword(s):  
Structure Elucidation ◽  
Three Dimensional ◽  
Data Bank ◽  
Competitive Inhibitor ◽  
Industrial Applications ◽  
Dimensional Structure ◽  
Full Understanding ◽  
The Poor ◽  
Computer Based ◽  
Inhibitory Agents

AbstractCassava is a strategic crop, especially for developing countries. However, the presence of cyanogenic compounds in cassava products limits the proper nutrients utilization. Due to the poor availability of structure discovery and elucidation in the Protein Data Bank is limiting the full understanding of the enzyme, how to inhibit it and applications in different fields. There is a need to solve the three-dimensional structure (3-D) of linamarase from cassava. The structural elucidation will allow the development of a competitive inhibitor and various industrial applications of the enzyme. The goal of this review is to summarize and present the available 3-D modeling structure of linamarase enzyme using different computational strategies. This approach could help in determining the structure of linamarase and later guide the structure elucidation in silico and experimentally.

MRPC (Missing Regions in Polypeptide Chains): a knowledgebase

2019 ◽  
Vol 52 (6) ◽  
pp. 1422-1426
Author(s):  
Rajendran Santhosh ◽  
Namrata Bankoti ◽  
Adgonda Malgonnavar Padmashri ◽  
Daliah Michael ◽  
Jeyaraman Jeyakanthan ◽  
...  
Keyword(s):  
Protein Structures ◽  
Three Dimensional ◽  
Protein Molecule ◽  
Data Bank ◽  
Protein Crystal ◽  
Dimensional Structure ◽  
Protein Structure Analysis ◽  
Three Dimensional Structure ◽  
X Ray Crystallography ◽  
Polypeptide Chains

Missing regions in protein crystal structures are those regions that cannot be resolved, mainly owing to poor electron density (if the three-dimensional structure was solved using X-ray crystallography). These missing regions are known to have high B factors and could represent loops with a possibility of being part of an active site of the protein molecule. Thus, they are likely to provide valuable information and play a crucial role in the design of inhibitors and drugs and in protein structure analysis. In view of this, an online database, Missing Regions in Polypeptide Chains (MRPC), has been developed which provides information about the missing regions in protein structures available in the Protein Data Bank. In addition, the new database has an option for users to obtain the above data for non-homologous protein structures (25 and 90%). A user-friendly graphical interface with various options has been incorporated, with a provision to view the three-dimensional structure of the protein along with the missing regions using JSmol. The MRPC database is updated regularly (currently once every three months) and can be accessed freely at the URL http://cluster.physics.iisc.ac.in/mrpc.

scholarly journals BLASTing away preconceptions in crystallization trials

2019 ◽  
Vol 75 (3) ◽  
pp. 184-192 ◽  
Author(s):  
Gabriel Jan Abrahams ◽  
Janet Newman
Keyword(s):  
Protein Data Bank ◽  
Sequence Similarity ◽  
Three Dimensional ◽  
Protein Sequences ◽  
Protein Molecule ◽  
Data Bank ◽  
Dimensional Structure ◽  
Critical Step ◽  
Quantitative Verification ◽  
Better Than

Crystallization is in many cases a critical step for solving the three-dimensional structure of a protein molecule. Determining which set of chemicals to use in the initial screen is typically agnostic of the protein under investigation; however, crystallization efficiency could potentially be improved if this were not the case. Previous work has assumed that sequence similarity may provide useful information about appropriate crystallization cocktails; however, the authors are not aware of any quantitative verification of this assumption. This research investigates whether, given current information, one can detect any correlation between sequence similarity and crystallization cocktails. BLAST was used to quantitate the similarity between protein sequences in the Protein Data Bank, and this was compared with three estimations of the chemical similarities of the respective crystallization cocktails. No correlation was detected between proteins of similar (but not identical) sequence and their crystallization cocktails, suggesting that methods of determining screens based on this assumption are unlikely to result in screens that are better than those currently in use.

scholarly journals SOLATION, CHARACTERIZATION, AND DOCKING STUDIES OF ISOLATED COMPOUNDS AS ANTIDIABETIC MOLECULES FROM CRESSA CRETICA

2020 ◽  
pp. 84-91
Author(s):  
SANGEETA RANI ◽  
KAVITA GAHLOT ◽  
ARVIND KUMAR
Keyword(s):  
Molecular Docking ◽  
Spectroscopic Analysis ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Lead Target ◽  
Coarse Powder ◽  
Autodock 4.0

Objective: The purpose of this study was to investigate the diabetic effect of phytocompounds isolated from Cressa cretica Linn. using spectroscopic analysis and molecular docking studies. Methods: Coarse powder of the whole plant of C. cretica was extracted with methanol, extracted part was subjected to silica column isolation, and two compounds: 2-Isopropyl-4-(1-methyl-dodeca-2,4-dienyloxy)-benzene-1,3,5-triol (Compound CN-01) and 11-Methyl-dodeca-2,4,6,8,10-pentenoic acid 2,3-dihydroxy-5-methyl-phenyl ester (Compound CN-02) were isolated in pure form. The three-dimensional structure of target protein was downloaded from PDB (www.rcsb.org) Protein Data Bank, Ligand file CN – 01 and CN – 02 were converted to MDL Molfile (V2000) format using ChemSketch 2017.2.1. These files could not be used directly in AutoDock 4.0 tools; thus, they were first converted to PDB files using an open babel tool. Results: Compounds were revealed through spectroscopic analysis and screened using AutoDock 4.0 tools. Docking study recommended that CN – 01 and CN – 02 an existing phytochemical from the plant of C. cretica had the highest fitness docking score and hence could be a potent antidiabetic drug. Conclusion: In this investigation, we docked the receptor (glycogen phosphorylase protein) holds a promising lead target formation against diabetes based on molecular docking analysis (minimum hydrogen bond length and maximum docked score). Thus, these compounds can be effectively used as drugs for treating diabetes which is predicted on the basis of docking scores.

Assembly states of the nucleosome assembly protein 1 (NAP-1) revealed by sedimentation velocity and non-denaturing MS

2011 ◽  
Vol 436 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Masanori Noda ◽  
Susumu Uchiyama ◽  
Adam R. McKay ◽  
Akihiro Morimoto ◽  
Shigeki Misawa ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Electrostatic Interactions ◽  
Analytical Ultracentrifugation ◽  
Three Dimensional ◽  
Sedimentation Velocity ◽  
Dimensional Structure ◽  
Histone H2a ◽  
Nucleosome Assembly ◽  
Nucleosome Assembly Protein ◽  
Nucleosome Assembly Protein 1

Proteins often exist as ensembles of interconverting states in solution which are often difficult to quantify. In the present manuscript we show that the combination of MS under nondenaturing conditions and AUC-SV (analytical ultracentrifugation sedimentation velocity) unambiguously clarifies a distribution of states and hydrodynamic shapes of assembled oligomers for the NAP-1 (nucleosome assembly protein 1). MS established the number of associated units, which was utilized as input for the numerical analysis of AUC-SV profiles. The AUC-SV analysis revealed that less than 1% of NAP-1 monomer exists at the micromolar concentration range and that the basic assembly unit consists of dimers of yeast or human NAP-1. These dimers interact non-covalently to form even-numbered higher-assembly states, such as tetramers, hexamers, octamers and decamers. MS and AUC-SV consistently showed that the formation of the higher oligomers was suppressed with increasing ionic strength, implicating electrostatic interactions in the formation of higher oligomers. The hydrodynamic shapes of the NAP-1 tetramer estimated from AUC-SV agreed with the previously proposed assembly models built using the known three-dimensional structure of yeast NAP-1. Those of the hexamer and octamer could be represented by new models shown in the present study. Additionally, MS was used to measure the stoichiometry of the interaction between the human NAP-1 dimer and the histone H2A–H2B dimer or H3–H4 tetramer. The present study illustrates a rigorous procedure for the analysis of protein assembly and protein–protein interactions in solution.

A murrel cysteine protease, cathepsin L: bioinformatics characterization, gene expression and proteolytic activity

Biologia ◽  
2014 ◽  
Vol 69 (3) ◽  
Author(s):  
Venkatesh Kumaresan ◽  
Prasanth Bhatt ◽  
Rajesh Palanisamy ◽  
Annie Gnanam ◽  
Mukesh Pasupuleti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacterial Infections ◽  
Cathepsin L ◽  
Three Dimensional ◽  
Structural Similarity ◽  
Data Bank ◽  
Minimum Free Energy ◽  
Dimensional Structure ◽  
Peptide Bonds ◽  
Gene Expression Studies

AbstractCathepsin L, a lysosomal endopeptidase, is a member of the peptidase C1 family (papain-like family) of cysteine proteinases that cleave peptide bonds of lysosomal proteins. In this study, we report a cathepsin L sequence identified from the constructed cDNA library of striped murrel Channa striatus (designated as CsCath L) using genome sequencing FLXTM technology. The full-length CsCath L contains three eukaryotic thiol protease domains at positions 134-145, 278-288 and 299-318. Phylogenetic analysis revealed that the CsCath L was clustered together with other cathepsin L from teleosts. The three-dimensional structure of CsCath L modelled by the I-Tasser program was compared with structures deposited in the Protein Data Bank to find out the structural similarity of CsCath L with experimentally identified structures. The results showed that the CsCath L exhibits maximum structural identity with pro-cathepsin L from human. The RNA fold structure of CsCath L was predicted along with its minimum free energy (−471.93 kcal/mol). The highest CsCath L gene expression was observed in liver, which was also significantly higher (P < 0.05) than that detected in other tissues taken for analysis. In order to investigate the mRNA transcription profile of CsCath L during infection, C. striatus were injected with fungus (Aphanomyces invadans) and bacteria (Aeromonas hydrophila) and its expression was up-regulated in liver at various time points. Similar to gene expression studies, the highest CsCath L enzyme activity was also observed in liver and its activity was up-regulated by fungal and bacterial infections.

TOP: a new method for protein structure comparisons and similarity searches

2000 ◽  
Vol 33 (1) ◽  
pp. 176-183 ◽  
Author(s):  
Guoguang Lu
Keyword(s):  
User Interface ◽  
Protein Structure ◽  
Protein Structures ◽  
Three Dimensional ◽  
Data Bank ◽  
Structure Alignment ◽  
Dimensional Structure ◽  
Protein Structure Alignment ◽  
Protein Structure Analysis ◽  
Structure Comparison

In order to facilitate the three-dimensional structure comparison of proteins, software for making comparisons and searching for similarities to protein structures in databases has been developed. The program identifies the residues that share similar positions of both main-chain and side-chain atoms between two proteins. The unique functions of the software also include database processingviaInternet- and Web-based servers for different types of users. The developed method and its friendly user interface copes with many of the problems that frequently occur in protein structure comparisons, such as detecting structurally equivalent residues, misalignment caused by coincident match of Cαatoms, circular sequence permutations, tedious repetition of access, maintenance of the most recent database, and inconvenience of user interface. The program is also designed to cooperate with other tools in structural bioinformatics, such as the 3DB Browser software [Prilusky (1998).Protein Data Bank Q. Newslett.84, 3–4] and the SCOP database [Murzin, Brenner, Hubbard & Chothia (1995).J. Mol. Biol.247, 536–540], for convenient molecular modelling and protein structure analysis. A similarity ranking score of `structure diversity' is proposed in order to estimate the evolutionary distance between proteins based on the comparisons of their three-dimensional structures. The function of the program has been utilized as a part of an automated program for multiple protein structure alignment. In this paper, the algorithm of the program and results of systematic tests are presented and discussed.

scholarly journals The htrA Gene Plays an Important role During Yersinia Pseudotuberculosis Growth at High Temperature

2020 ◽  
Author(s):  
Elena Escobar Garduño ◽  
Lucia Soto Urzua ◽  
Rogelio Rodriguez Sotres ◽  
Luis Javier Martinez Morales
Keyword(s):  
Growth Rate ◽  
Mutant Strain ◽  
Growth Rates ◽  
Yersinia Pseudotuberculosis ◽  
Wild Strain ◽  
Three Dimensional ◽  
Data Bank ◽  
Immunoblot Analysis ◽  
Dimensional Structure ◽  
Bacteria Growth

Abstract htrA is a gene coding for the stress inducible HtrA protein, identified as a temperature stress response protein in several Gram positive and Gram negative bacteria. Growth rates at several temperatures (30ºC, 37ºC and 42ºC) were compared for Yersinia pseudotuberculosis YPIII wild strain and the isogenic mutant 1YPIII (htrA::Km), which was obtained by insertion of a kanamycin resistance cassette into the htrA gene.Y. pseudotuberculosis 1YPIII growth rates did not differ from the Y. pseudotuberculosis wild strain growth rates when cultivated at 30°C, which is consistent with a non-essential role for the HtrA protein at this temperature. However, 1YPIII mutant strain growth rate decreased by 18.73% at 37°C, and by 60.14% at 42°C, as compared to the Y. pseudotuberculosis YPIII wild strain growth rate. HtrA complementation in the strain 1YPIII/pAHTRA46 suppressed the differences in growth rates. Immunoblot analysis confirmed the absence of the HtrA protein in the 1YPIII mutant strain at any of the growth temperatures under analysis. In silico predictions were obtained for the three-dimensional structure of amino acid sequence belonging to HtrA from Y. pseudotuberculosis YPIII, Yersinia pestis CO92, using the protein data bank structure 1KY9:B from Escherichia coli, as template. The model's quality was found to be acceptable. Southern blot analysis shows a single htrA gene signal. These data indicate that the unique htrA gene in Y. pseudotuberculosis YPIII is required for the adaptive response of this species to high temperatures and although it is not a pathogenicity factor, it can be targeted by antibiotics.

scholarly journals Protein Interaction Z Score Assessment (PIZSA): an empirical scoring scheme for evaluation of protein–protein interactions

2019 ◽  
Vol 47 (W1) ◽  
pp. W331-W337 ◽  
Author(s):  
Ankit A Roy ◽  
Abhilesh S Dhawanjewar ◽  
Parichit Sharma ◽  
Gulzar Singh ◽  
M S Madhusudhan
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Optimal Number ◽  
Dimensional Structure ◽  
Side Chain ◽  
Interface Residue ◽  
Z Score ◽  
Protein Protein Interactions ◽  
Residue Contacts

Abstract Our web server, PIZSA (http://cospi.iiserpune.ac.in/pizsa), assesses the likelihood of protein–protein interactions by assigning a Z Score computed from interface residue contacts. Our score takes into account the optimal number of atoms that mediate the interaction between pairs of residues and whether these contacts emanate from the main chain or side chain. We tested the score on 174 native interactions for which 100 decoys each were constructed using ZDOCK. The native structure scored better than any of the decoys in 146 cases and was able to rank within the 95th percentile in 162 cases. This easily outperforms a competing method, CIPS. We also benchmarked our scoring scheme on 15 targets from the CAPRI dataset and found that our method had results comparable to that of CIPS. Further, our method is able to analyse higher order protein complexes without the need to explicitly identify chains as receptors or ligands. The PIZSA server is easy to use and could be used to score any input three-dimensional structure and provide a residue pair-wise break up of the results. Attractively, our server offers a platform for users to upload their own potentials and could serve as an ideal testing ground for this class of scoring schemes.

Three-dimensional structure of a regular bacterial surface layer: The HPI-layer of Deinococcus radiodurans

1983 ◽  
Vol 41 ◽  
pp. 438-439
Author(s):  
W. Baumeister ◽  
M. Hahn ◽  
W.O. Saxton
Keyword(s):  
Outer Membrane ◽  
Protein Interactions ◽  
Deinococcus Radiodurans ◽  
Bacterial Species ◽  
Hexagonal Lattice ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Protein Protein Interactions ◽  
Bacterial Surface ◽  
Freeze Dried

Regularly organized surface (RS) layers are a feature common to many bacterial species; they are clearly more abundant than was anticipated even a few years ago. The RS-layers are believed to fulfil a variety of functions in the interaction between the cell and its environment (see e.g. [1]). The so-called HPI-layer of the radiotolerant bacterium Deinococcus radiodurans is a typical example of such a layer: It is composed of a single polypeptide species (Mr 105 kDa) arranged on a hexagonal lattice to form a network that covers the entire surface of the bacterium; it is associated with the outer membrane via hydrophobic protein-protein interactions.Isolated HPI-layer sheets, released from the outer membrane by detergent treatment, have been studied in the electron microscope making extensive use of the present arsenal of preparation techniques: negative staining, (auro- thio)glucose embedding, freeze-dried/unstained, freeze-dried/metal shadowed etc.Because of the notorious problem of lattice imperfections image processing usually followed the strategy of correlation averaging as outlined in some detail elsewhere.

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