scholarly journals AtTRB1–3 Mediates Structural Changes in AtPOT1b to Hold ssDNA

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Amit Jaiswal
Keyword(s):  
Arabidopsis Thaliana ◽  
Molecular Docking ◽  
Structural Modification ◽  
Essential Role ◽  
Structural Changes ◽  
Conformational Dynamics ◽  
Genomic Stability ◽  
Telomeric Dna ◽  
Rich Region ◽  
Docking Interaction

POT from Arabidopsis thaliana is a member of shelterin complex and belongs to Telo_bind protein family. Three homologs are reported, namely, AtPOT1a, AtPOT1b, and AtPOT1c, where AtPOT1b is involved in genomic stability and chromosome end protection by providing necessary grip to G-rich region of telomeric DNA for telomerase assembly. Telomeric binding factors (TRB1–3) physically interact with POT with no known functionality. In this work attempt has been made to elucidate the reason behind the interaction by analyzing molecular docking interaction between AtPOT1b and AtTRB1–3, which yielded potential residues, which could play essential role in structural modification. 3 ns molecular simulation helped to look into structural stability and conformational dynamics portraying domain movements. AtTRB’s interaction with AtPOT1b provoked structural changes in AtPOT1b, thereby increasing the affinity for single strand DNA (ssDNA) as compared to double strand DNA (dsDNA). Although the obtained results require experimental evidence they can act as a guide in tracing the functions in other organisms. The information provided in this paper would be helpful in understanding functions of TRB1–3 with respect to genomic stability.

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>

NMR structure and conformational dynamics of AtPDFL2.1, a defensin-like peptide from Arabidopsis thaliana

2016 ◽  
Vol 1864 (12) ◽  
pp. 1739-1747 ◽  
Author(s):  
Reza Omidvar ◽  
Youlin Xia ◽  
Fernando Porcelli ◽  
Holger Bohlmann ◽  
Gianluigi Veglia
Keyword(s):  
Arabidopsis Thaliana ◽  
Conformational Dynamics ◽  
Nmr Structure

Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Yeast

2021 ◽  
Author(s):  
Nicole J. Wayne ◽  
Katherine E. Dembny ◽  
Tyler Pease ◽  
Farrin Saba ◽  
Xiaohong Zhao ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Essential Role ◽  
Marked Effect ◽  
Yeast Prion ◽  
Rich Region ◽  
Polyglutamine Repeat ◽  
Prion Propagation

The aggregation of huntingtin fragments with expanded polyglutamine repeat regions (HttpolyQ) that cause Huntington’s disease depends on the presence of a prion with an amyloid conformation in yeast. As a result of this relationship, HttpolyQ aggregation indirectly depends on Hsp104 due to its essential role in prion propagation. We find that HttQ103 aggregation is directly affected by Hsp104 with and without the presence of [ RNQ + ] and [ PSI + ] prions. When we inactivate Hsp104 in the presence of prion, yeast have only one or a few large HttQ103 aggregates rather than numerous smaller aggregates. When we inactivate Hsp104 in the absence of prion, there is no significant aggregation of HttQ103; whereas with active Hsp104, HttQ103 aggregates slowly accumulate due to the severing of spontaneously nucleated aggregates by Hsp104. We do not observe either effect with HttQ103P, which has a polyproline-rich region downstream of the polyglutamine region, because HttQ103P does not spontaneously nucleate and Hsp104 does not efficiently sever the prion-nucleated HttQ103P aggregates. Therefore, the only role of Hsp104 in HttQ103P aggregation is to propagate yeast prion. In conclusion, because Hsp104 efficiently severs the HttQ103 aggregates, but not HttQ103P aggregates, it has a marked effect on the aggregation of HttQ103, but not HttQ103P.

scholarly journals DNA Polymerase: Structural Homology, Conformational Dynamics, and the Effects of Carcinogenic DNA Adducts

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Richard G. Federley ◽  
Louis J. Romano
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Dna Adducts ◽  
Structural Changes ◽  
Dna Polymerases ◽  
Conformational Dynamics ◽  
Three Dimensional ◽  
Structural Homology ◽  
Human Right ◽  
Selection Of

DNA replication is vital for an organism to proliferate and lying at the heart of this process is the enzyme DNA polymerase. Most DNA polymerases have a similar three dimensional fold, akin to a human right hand, despite differences in sequence homology. This structural homology would predict a relatively unvarying mechanism for DNA synthesis yet various polymerases exhibit markedly different properties on similar substrates, indicative of each type of polymerase being prescribed to a specific role in DNA replication. Several key conformational steps, discrete states, and structural moieties have been identified that contribute to the array of properties the polymerases exhibit. The ability of carcinogenic adducts to interfere with conformational processes by directly interacting with the protein explicates the mutagenic consequences these adducts impose. Recent studies have identified novel states that have been hypothesised to test the fit of the nascent base pair, and have also shown the enzyme to possess a lively quality by continually sampling various conformations. This review focuses on the homologous structural changes that take place in various DNA polymerases, both replicative and those involved in adduct bypass, the role these changes play in selection of a correct substrate, and how the presence of bulky carcinogenic adducts affects these changes.

scholarly journals Enzyme-Site Blocking Combined with Optimization of Molecular Docking for Efficient Discovery of Potential Tyrosinase Specific Inhibitors from Puerariae lobatae Radix

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2612 ◽  
Author(s):  
Haichun Liu ◽  
Yitian Zhu ◽  
Ting Wang ◽  
Jin Qi ◽  
Xuming Liu
Keyword(s):  
Molecular Docking ◽  
Structural Modification ◽  
Enzyme Inhibitors ◽  
Kojic Acid ◽  
Systematic Evaluation ◽  
Tyrosinase Inhibition ◽  
Computational Docking ◽  
Site Blocking ◽  
Leading Compounds ◽  
Positive Results

Enzyme inhibitors from natural products are becoming an attractive target for drug discovery and development; however, separating enzyme inhibitors from natural-product extracts is highly complex. In this study, we developed a strategy based on tyrosinase-site blocking ultrafiltration integrated with HPLC-QTOF-MS/MS and optimized molecular docking to screen tyrosinase inhibitors from Puerariae lobatae Radix extract. Under optimized ultrafiltration parameters, we previously used kojic acid, a known tyrosinase inhibitor, to block the tyrosinase active site in order to eliminate false-positive results. Using this strategy, puerarin, mirificin, daidzin and genistinc were successfully identified as potential ligands, and after systematic evaluation by several docking programs, the rank of the identified compounds predicted by computational docking was puerarin > mirificin > kojic acid > daidzin ≈ genistin, which agreed with the results of tyrosinase-inhibition assays. Structure-activity relationships indicated that C-glycosides showed better tyrosinase inhibition as compared with O-glycosides, with reduced inhibition achieved through the addition of glycosyl, which provides ideas about the screen of leading compounds and structural modification.

Interaction study of ciprofloxacin with human telomeric DNA by spectroscopy and molecular docking

2013 ◽  
Vol 107 ◽  
pp. 227-234 ◽  
Author(s):  
Huihui Li ◽  
Xiaoyang Bu ◽  
Jia Lu ◽  
Chongzheng Xu ◽  
Xianlong Wang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Interaction Study ◽  
Telomeric Dna

scholarly journals Genomic stability in Arabidopsis thaliana transgenic plants obtained by floral dip

2004 ◽  
Vol 109 (7) ◽  
pp. 1512-1518 ◽  
Author(s):  
M. Labra ◽  
C. Vannini ◽  
F. Grassi ◽  
M. Bracale ◽  
M. Balsemin ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transgenic Plants ◽  
Genomic Stability ◽  
Floral Dip

From folding to function: complex macromolecular reactions unraveled one-by-one with optical tweezers

2021 ◽  
Author(s):  
Pétur O. Heidarsson ◽  
Ciro Cecconi
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Conformational Dynamics ◽  
Disordered Proteins ◽  
Kinase Activation ◽  
Intrinsically Disordered ◽  
Complex Protein ◽  
Methodological Principles

Abstract Single-molecule manipulation with optical tweezers has uncovered macromolecular behaviour hidden to other experimental techniques. Recent instrumental improvements have made it possible to expand the range of systems accessible to optical tweezers. Beyond focusing on the folding and structural changes of isolated single molecules, optical tweezers studies have evolved into unraveling the basic principles of complex molecular processes such as co-translational folding on the ribosome, kinase activation dynamics, ligand–receptor binding, chaperone-assisted protein folding, and even dynamics of intrinsically disordered proteins (IDPs). In this mini-review, we illustrate the methodological principles of optical tweezers before highlighting recent advances in studying complex protein conformational dynamics – from protein synthesis to physiological function – as well as emerging future issues that are beginning to be addressed with novel approaches.

STRUCTURAL CHANGES ASSOCIATED WITH THE RELEASE OF ENZYMES FROM RAT-LIVER MITOCHONDRIA BY FREEZING

1966 ◽  
Vol 44 (6) ◽  
pp. 775-781 ◽  
Author(s):  
C. V. Lusena ◽  
C. M. S. Dass
Keyword(s):  
Rat Liver ◽  
Structural Modification ◽  
Structural Changes ◽  
Sodium Deoxycholate ◽  
Liver Mitochondria ◽  
Maximum Activity ◽  
Supernatant Fraction ◽  
Rat Liver Mitochondria ◽  
Mitochondrial Disruption ◽  
Partial Release

Suspensions of rat-liver mitochondria in 0.44 M sucrose, after they were frozen and thawed under defined conditions, were partitioned into three sedimentable and one supernatant fraction by differential centrifugation. These were analyzed for optical density, protein content, and for activities of glutamate dehydrogenase (GD) and 3-hydroxybutyrate dehydrogenase (BD) with exogenous nicotinamide–adenine dinucleotide (NAD) both as maximum activity after sodium deoxycholate treatment and as activity released by freezing. Pellets of the three sedimentable fractions were also examined in the electron microscope. When dehydrogenases were not released by a freezing treatment, no structural changes were detected. Release of BD, which was accompanied by release of GD as well, was associated with mitochondrial disruption and drastic rearrangement of mitochondrial membranes. On the other hand, release of GD without BD occurred from swollen and emptied mitochondria. The partial release of enzymes in a preparation was not associated with a partial structural modification of all of the mitochondria, but rather with drastic structural changes in only some of them.

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