Hyperthermophilic dehydrogenase enzymes

2004 ◽  
Vol 32 (2) ◽  
pp. 255-258 ◽  
Author(s):  
J.A. Littlechild ◽  
J.E. Guy ◽  
M.N. Isupov
Keyword(s):  
Hydrophobic Interactions ◽  
Specific Class ◽  
Protein Chain ◽  
Salt Bridges ◽  
Sequence Identity ◽  
Dehydrogenase Enzyme ◽  
Different Types ◽  
Methanothermus Fervidus ◽  
Crystallographic Structures ◽  
Quaternary Complex

Archaeal dehydrogenases are often found to be of a specific class of dehydrogenase which has low sequence identity to the equivalent bacterial and eukaryotic counterparts. This paper focuses on two different types of hyperthermophilic dehydrogenase enzyme that have been cloned and over-expressed in Escherichia coli. The crystallographic structures of the apo form of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) from Sulfolobus solfataricus and the related holo form of GAPDH from Methanothermus fervidus have been solved to high resolution. The zinc-containing structure of ADH (alcohol dehydrogenase) from Aeropyrum pernix has also been solved as a quaternary complex with the cofactor NADH and the inhibitor octanoic acid. The results show that despite the low sequence identity to the related enzymes found in other organisms the fold of the protein chain is similar. The archaeal GAPDH enzymes show a relocation of the active site which is a feature of evolutionary interest. The high thermostability of these three archaeal dehydrogenases can be attributed to a combination of factors including an increase in the number of salt bridges and hydrophobic interactions, a higher percentage of secondary structure and the presence of disulphide bonds.

scholarly journals Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 23 ◽  
Author(s):  
Martijn Selten ◽  
Hans van Bokhoven ◽  
Nael Nadif Kasri
Keyword(s):  
Psychiatric Disorders ◽  
Relative Strength ◽  
Inhibitory Neurons ◽  
Specific Class ◽  
Post Mortem ◽  
Inhibitory System ◽  
Network Function ◽  
Different Types ◽  
Flow Of Information

Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.

Factor XI Homodimer Formation Is Mediated by Electrostatic (Lys331 with Glu287) and Hydrophobic (Ile290 with Leu284 and Tyr329 with Tyr329) Interactions in the Apple 4 Domain and Is Essential for Normal Proteolytic Activation of Factor XI by Factor XIIa, Thrombin and Factor XIa.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2706-2706
Author(s):  
Wenman Wu ◽  
Dipali Sinha ◽  
James D. Lear ◽  
Paul C. Billings ◽  
Peter N. Walsh
Keyword(s):  
Disulfide Bond ◽  
Analytical Ultracentrifugation ◽  
Hydrophobic Interactions ◽  
The Other ◽  
Size Exclusion ◽  
Hek293 Cells ◽  
Salt Bridges ◽  
Factor Xi ◽  
Proteolytic Activation ◽  
Interchain Disulfide Bond

Abstract Factor XI (FXI), a coagulation protein essential for normal hemostasis, is a homodimer consisting of two identical subunits of 80 KDa linked by a disulfide bond formed by Cys321 within the Apple 4 (A4) domain of each subunit. Prekallikrein (PK), in spite of its high homology with FXI both in amino acid sequence and domain structure, is a monomer. Cys321 in PK forms an intrachain disulfide bond with Cys326. However FXI/C321S (in which interchain disulfide bond formation is precluded) is a noncovalent dimer. Thus, there are interacting residues between the two subunits of FXI that are responsible for mediating its unique homodimeric structure. Examination of the crystal structure of FXI (Papagrigoriou E, McEwan P, Walsh PN, Emsley J. Nature Structural & Molecular Biology. 2006;13:557–8) shows salt bridges between Lys331 of one subunit with Glu287 of the other subunit as well as hydrophobic interactions at the interface of the A4 domains involving Ile290, Leu284 and Tyr329. FXI/C321S, FXI/C321S/K331A, FXI/C321S/E287A, FXI/C321S/I290A, FXI/C321S/Y329A, FXI/C321S/L284A and FXI/C321S/K331R were expressed in HEK293 cells and characterized using size exclusion chromatography (SEC), analytical ultracentrifugation (AUC), and functional assays. Whereas FXI/C321S existed in a monomer/dimer equilibrium (Kd ∼40 nM) all other mutants were predominantly monomers by SEC with impaired dimer formation by AUC (Kd 3.4–38 μM). All the monomeric mutants when converted to the active enzyme, FXIa, were able to hydrolyze the small chromogenic substrate S-2366 with normal values of Km and Vmax and cleaved the macromolecular substrate FIX at both its scissile bonds at rates similar to those observed with wtFXIa strongly suggesting that all mutant proteins were properly folded. However all the monomeric mutants displayed impaired clotting activity in an APTT assay and displayed markedly decreased rates of activation by FXIIa or thrombin and autoactivation in the presence or absence of dextran sulfate. We conclude that salt bridges formed between Lys331 of one subunit and Glu287 of the other together with hydrophobic interactions of residues Ile290 with Leu284 and Tyr329 with Tyr329 and are essential for normal homodimer formation, which is essential for normal proteolytic activation of FXI by FXIIa, thrombin and FXIa either in solution or on an anionic surface.

scholarly journals Mutational Analysis of Differences in Thermostability between Histones from Mesophilic and Hyperthermophilic Archaea

2000 ◽  
Vol 182 (3) ◽  
pp. 812-817 ◽  
Author(s):  
Wen-Tyng Li ◽  
John W. Shriver ◽  
John N. Reeve
Keyword(s):  
Mutational Analysis ◽  
Hydrophobic Interactions ◽  
Ion Pairs ◽  
Histone Variants ◽  
Random Coil ◽  
Hyperthermophilic Archaea ◽  
Amino Acid Residues ◽  
Methanothermus Fervidus ◽  
Model Dimer ◽  
Archaeal Histone

ABSTRACT Amino acid residues responsible for the large difference in thermostability between HMfB and HFoB, archaeal histones from the hyperthermophile Methanothermus fervidus and the mesophileMethanobacterium formicicum, respectively, have been identified by site-specific mutagenesis. The thermal denaturation of ∼70 archaeal histone variants has been monitored by circular dichroism, and the data generated were fit to a two-state unfolding model (dimer→two random coil monomers) to obtain a standard-state (1M) melting temperature for each variant dimer. The results of single-, double-, and triple-residue substitutions reveal that the much higher stability of rHMfB dimers, relative to rHFoB dimers, is conferred predominantly by improved intermolecular hydrophobic interactions near the center of the histone dimer core and by additional favorable ion pairs on the dimer surface.

scholarly journals Thyroid stimulating autoantibody M22 mimics TSH binding to the TSH receptor leucine rich domain: a comparative structural study of protein–protein interactions

2009 ◽  
Vol 42 (5) ◽  
pp. 381-395 ◽  
Author(s):  
R Núñez Miguel ◽  
J Sanders ◽  
D Y Chirgadze ◽  
J Furmaniak ◽  
B Rees Smith
Keyword(s):  
Crystal Structure ◽  
Protein Interactions ◽  
Hydrophobic Interactions ◽  
Human Monoclonal Antibody ◽  
Tsh Receptor ◽  
Salt Bridges ◽  
Protein Protein Interactions ◽  
Rich Domain ◽  
Candidate Target ◽  
Comparative Model

The TSH receptor (TSHR) ligands M22 (a thyroid stimulating human monoclonal antibody) and TSH, bind to the concave surface of the leucine rich repeats domain (LRD) of the TSHR and here, we show that M22 mimics closely the binding of TSH. We compared interactions produced by M22 with the TSHR in the M22–TSHR crystal structure (2.55 Å resolution) and produced by TSH with the TSHR in a TSH–TSHR comparative model. The crystal structure of the TSHR and a comparative model of TSH based on the crystal structure of FSH were used as components to build the TSH–TSHR model. This model was built based on the FSH–FSH receptor structure (2.9 Å) and then the structure of the TSHR in the model was replaced by the TSHR crystal structure. The analysis shows that M22 light chain mimics the TSHβ chain in its interaction with TSHR LRD, while M22 heavy chain mimics the interactions of the TSHα chain. The M22–TSHR complex contains a greater number of hydrogen bonds and salt bridges and fewer hydrophobic interactions than the TSH–TSHR complex, consistent with a higher M22 binding affinity. Furthermore, the surface area formed by TSHR residues N208, Q235, R255, and N256 has been identified as a candidate target region for small molecules which might selectively block binding of autoantibodies to the TSHR.

scholarly journals The application of biogas fermentation digestate as soil fertilizer

2020 ◽  
Vol 14 (1) ◽  
pp. 76-81
Author(s):  
Klára Czakó-Vér ◽  
Dávid Somfai ◽  
Erzsébet Suhajda ◽  
Márk Strasszer ◽  
Gyula Árvay ◽  
...  
Keyword(s):  
Hydrogen Transfer ◽  
Arable Land ◽  
Soil Protection ◽  
Meadow Soil ◽  
Critical Aspect ◽  
Brown Forest Soil ◽  
Dehydrogenase Enzyme ◽  
Biogas Digestate ◽  
Different Types ◽  
Biogas Plants

As organic manure is becoming less available, using different materials as soil fertilizers and the application of the inorganic fertilizers raises many questions. Therefore, it is increasingly important to use compost and biogas digestate to improve soil quality. The activity of the microbial communities ensures the fertility of the soil. One of the most important enzymes is dehydrogenase. This enzyme group catalyses the hydrogen transfer in the process of biological oxidation. Our aim was to examine the effect of biogas digestate on dehydrogenase enzyme activity (DHA) in 3 different types of soil. Hungarian standard method was used to evaluate DHA. The applied biogas digestate was obtained from the Kaposvár Sugar Factory of Hungarian Sugar Ltd. The dose is equal to 16,7 m3ha-1 and 533 kg organic matterha-1. The treatment was performed in three different groups of soil: brown forest soil, calcareous chernozem and carbonate meadow soil. The results showed an increase in DHA in all types of soil. DHA values were the highest in case of the carbonate meadow soil, specifically 0.337 mg formazan/1 g soil/24 h immediately after the treatment and 0.410 after 28 days. A critical aspect to consider during the construction of biogas plants is the soil protection agency’s ban on using soil fertilizers during the winter months. Analysis carried out according to the protocol of sewage sludge examination revealed that biofermentate produced during biogas generation does not contain any environmentally harmful components. After the elaboration of a soil protection plan, the recommended way to apply biogas digestate to arable land is via injectors.  

scholarly journals The Immobilization of ChEMBL474807 Molecules Using Different Classes of Nanostructures

Symmetry ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 980 ◽  
Author(s):  
Przemysław Czeleń ◽  
Beata Szefler
Keyword(s):  
Hydrophobic Interactions ◽  
Dominant Role ◽  
Fullerene C60 ◽  
C60 Fullerene ◽  
Ligand Molecule ◽  
Structural Modifications ◽  
Different Types ◽  
C60 Derivatives ◽  
Stacking And Hydrophobic Interactions ◽  
Cancer Diseases

Indirubin derivatives and analogues are a large group of compounds which are widely and successfully used in treatment of many cancer diseases. In particular, the ChEMBL474807 molecule, which has confirmed inhibiting abilities against CDK2 and GSK3B enzymes, can be included in this group. The immobilization of inhibitors with the use of nanocarriers is an often used strategy in creation of targeted therapies. Evaluations were made of the possibility of immobilizing ligand molecules on different types of nanocarrier, such as carbon nanotubes (CNT), functionalized fullerene C60 derivatives (FF_X), and functionalized cube rhombellanes, via the use of docking methods. All results were compared with a reference system, namely C60 fullerene. The realized calculations allowed indication of a group of compounds that exhibited significant binding affinity relative to the ligand molecule. Obtained data shows that structural modifications, such as those related to the addition of functional groups or changes of structure symmetry, realized in particular types of considered nanostructures, can contribute to increases of their binding capabilities. The analysis of all obtained nano complexes clearly shows that the dominant role in stabilization of such systems is played by stacking and hydrophobic interactions. The realized research allowed identification of potential nanostructures that, together with the ChEMBL474807 molecule, enable the creation of targeted therapy.

scholarly journals Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol

2016 ◽  
Vol 114 (2) ◽  
pp. 206-214 ◽  
Author(s):  
Rameshwar U. Kadam ◽  
Ian A. Wilson
Keyword(s):  
Influenza Virus ◽  
Broad Spectrum ◽  
Hydrophobic Interactions ◽  
Antiviral Drug ◽  
Binding Mode ◽  
Influenza Viruses ◽  
Structural Basis ◽  
Salt Bridges ◽  
Fusion Inhibition ◽  
Conformational Rearrangements

The broad-spectrum antiviral drug Arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (HA) fusion machinery. However, the structural basis of the mechanism underlying fusion inhibition by Arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. We determined crystal structures of Arbidol in complex with influenza virus HA from pandemic 1968 H3N2 and recent 2013 H7N9 viruses. Arbidol binds in a hydrophobic cavity in the HA trimer stem at the interface between two protomers. This cavity is distal to the conserved epitope targeted by broadly neutralizing stem antibodies and is ∼16 Å from the fusion peptide. Arbidol primarily makes hydrophobic interactions with the binding site but also induces some conformational rearrangements to form a network of inter- and intraprotomer salt bridges. By functioning as molecular glue, Arbidol stabilizes the prefusion conformation of HA that inhibits the large conformational rearrangements associated with membrane fusion in the low pH of the endosome. This unique binding mode compared with the small-molecule inhibitors of other class I fusion proteins enhances our understanding of how small molecules can function as fusion inhibitors and guides the development of broad-spectrum therapeutics against influenza virus.

Micro-flow assisted synthesis of fluorescent polymer nanoparticles with tuned size and surface properties

2016 ◽  
Vol 5 (2) ◽  
Author(s):  
Nikunjkumar Visaveliya ◽  
Christian Hoffmann ◽  
Alexander Groß ◽  
Eric Täuscher ◽  
Uwe Ritter ◽  
...  
Keyword(s):  
Surface Charge ◽  
Hydrophobic Interactions ◽  
Spherical Shape ◽  
Spectroscopic Properties ◽  
Polymer Nanoparticles ◽  
Surface Immobilization ◽  
Different Types ◽  
Minimum Number ◽  
Micro Flow ◽  
Fluorescent Polymer

AbstractNumerous different photonics and biomedical applications depend on the fluorescent polymer micro- and nanoparticles. Besides optical or spectroscopic properties, the performance of the polymer nanoparticles is determined by their size, size distribution, and surface charge. Moreover, in order to realize a very uniform performance, the functional polymer nanoparticles should be of high homogeneity and demand for the preparation in a minimum number of synthesis steps. Here, we present a microfluidic-assisted synthesis of different types of reproducible fluorescent polymer nanoparticles with tuned size (40 nm up to 600 nm) and surface charge (ζ potential=-52 mV up to +45 mV). Four different preparation strategies were introduced for fluorophore-functionalized nanoparticles: (a) noncovalent binding of fluorophores with high loading, (b) covalent linking of fluorophores with enhanced stability, (c) surface-anchored fluorophores by hydrophobic interactions for triple function at the same time, and (d) surface immobilization of biomolecules and fluorophore by ionic as well as secondary interactions. In this way, four different classes of nanoparticles suited for different applications were prepared with a spherical shape as a model system. Moreover, the principle has been extended to the different types of nonspherical and composite polymer nanoparticles.

Conservation of Amino Acids into Multiple Alignments Involved in Pairwise Interactions in Three-Dimensional Protein Structures

2003 ◽  
Vol 01 (03) ◽  
pp. 505-520 ◽  
Author(s):  
Mounir Errami ◽  
Christophe Geourjon ◽  
Gilbert Deléage
Keyword(s):  
Amino Acids ◽  
Disulfide Bonds ◽  
Hydrophobic Interactions ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Features ◽  
Multiple Alignment ◽  
Salt Bridges ◽  
Multiple Alignments ◽  
Multiple Sequences

We present an original strategy, that involves a bioinformatic software structure, in order to perform an exhaustive and objective statistical analysis of three-dimensional structures of proteins. We establish the relationship between multiple sequences alignments and various structural features of proteins. We show that amino acids implied in disulfide bonds, salt bridges and hydrophobic interactions are particularly conserved. Effects of identity, global similarity within alignments, and accessibility of interactions have been studied. Furthermore, we point out that the more variable the sequences within a multiple alignment, the more informative the multiple alignment. The results support multiple alignments usefulness for predictions of structural features.

Role of hydrophobic interactions and salt-bridges in β-hairpin folding

2005 ◽  
Vol 12 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Aswin Sai Narain Seshasayee ◽  
Krishnan Raghunathan ◽  
Karthikeyan Sivaraman ◽  
Gautam Pennathur
Keyword(s):  
Hydrophobic Interactions ◽  
Salt Bridges
Sign in / Sign up

Export Citation Format

Share Document