Coronaviral methyltransferases (MTases), nsp10/16 and nsp14, catalyze the last two steps of viral RNA-cap creation that takes place in cytoplasm. This cap is essential for the stability of viral RNA and, most importantly, for the evasion of innate immune system. Non-capped RNA is recognized by innate immunity which leads to its degradation and the activation of antiviral immunity. As a result, both coronaviral MTases are in the center of scientific scrutiny. Recently, X-ray and cryo-EM structures of both enzymes were solved even in complex with other parts of the viral replication complex. High-throughput screening as well as structure-guided inhibitor design have led to the discovery of their potent inhibitors. Here, we critically summarize the tremendous advancement of the coronaviral MTase field since the beginning of COVID pandemic.

• MeSH
• aminokyseliny chemie   MeSH
• Coronavirus účinky léků   enzymologie   genetika   MeSH
• lidé MeSH
• methyltransferasy antagonisté a inhibitory   chemie   metabolismus   MeSH
• metylace MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• objevování léků MeSH
• RNA virová chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• methyltransferasy MeSH
• RNA virová MeSH

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers, but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review, we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

• Klíčová slova
• DNA:RNA hybrid, G-quadruplex, R-loop, dimer, multimer, oligomer, promoter, telomere, tetramer,
• MeSH
• DNA chemie   MeSH
• G-kvadruplexy * MeSH
• konformace nukleové kyseliny * MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• RNA chemie   MeSH
• telomery MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• DNA MeSH
• RNA MeSH

Since the dawn of quantitative structure-properties relationships (QSPR), empirical parameters related to structural, electronic and hydrophobic molecular properties have been used as molecular descriptors to determine such relationships. Among all these parameters, Hammett sigma constants and the logarithm of the octanol-water partition coefficient, log P, have been massively employed in QSPR studies. In the present paper, a new molecular descriptor, based on quantum similarity measures (QSM), is proposed as a general substitute of these empirical parameters. This work continues previous analyses related to the use of QSM to QSPR, introducing molecular quantum self-similarity measures (MQS-SM) as a single working parameter in some cases. The use of MQS-SM as a molecular descriptor is first confirmed from the correlation with the aforementioned empirical parameters. The Hammett equation has been examined using MQS-SM for a series of substituted carboxylic acids. Then, for a series of aliphatic alcohols and acetic acid esters, log P values have been correlated with the self-similarity measure between density functions in water and octanol of a given molecule. And finally, some examples and applications of MQS-SM to determine QSAR are presented. In all studied cases MQS-SM appeared to be excellent molecular descriptors usable in general QSPR applications of chemical interest.

• MeSH
• kvantová teorie MeSH
• molekulární struktura MeSH
• vztahy mezi strukturou a aktivitou * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The emergence of graphene in recent years provides exciting avenues for achieving fast, reliable DNA/RNA sensing and sequencing. Here we explore the possibility of enhancing electronic fingerprints of nucleobases adsorbed on graphene by tuning the surface coverage and modifying molecular dipoles using first-principles calculations. We demonstrate that intermolecular interactions have a strong influence on the adsorption geometry and the electronic structure of the nucleobases, resulting in tilted configurations and a considerable modification of their electronic fingerprints in graphene. Our analysis reveals that the molecular dipole of the nucleobase molecules plays a dominant role in the electronic structure of graphene-nucleobase systems, inducing significant changes in the work functions and energy level alignments at the interface. These results highlight tunable control of the measured molecular signals in graphene by optimizing the surface contact between nucleobases and graphene. Our findings have important implications for identification and understanding of molecular fingerprints of DNA/RNA nucleobases in graphene-based sensing and sequencing methods.

• MeSH
• DNA chemie   MeSH
• grafit chemie   MeSH
• molekulární modely * MeSH
• molekulární struktura MeSH
• RNA chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• grafit MeSH
• RNA MeSH

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of the normal modes of vibrations was done using GAR2PED program. (1)H NMR chemical shifts calculations were carried out by using B3LYP functional with SDD basis set. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. MEP was performed by the DFT method and the predicted infrared intensities and Raman activities have also been reported. The calculated geometrical parameters are in agreement with that of similar derivatives. The title compound forms a stable complex with PknB as is evident from the binding affinity values and the molecular docking results suggest that the compound might exhibit inhibitory activity against PknB and this may result in development of new anti-tuberculostic agents.

• Klíčová slova
• DFT, FT-IR, FT-Raman, MEP, Molecular docking, Quinoline,
• MeSH
• chinoliny chemie   MeSH
• kvantová teorie * MeSH
• kyseliny karboxylové chemie   MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• Ramanova spektroskopie metody   MeSH
• simulace molekulového dockingu MeSH
• spektrofotometrie ultrafialová MeSH
• spektroskopie infračervená s Fourierovou transformací metody   MeSH
• statická elektřina MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-((E)-2-(2-bromophenyl)ethenyl)quinoline-6-carboxylic acid MeSH Prohlížeč
• chinoliny MeSH
• kyseliny karboxylové MeSH

Comparative evolutionary genomics has revealed that novel protein coding genes can emerge randomly from non-coding DNA. While most of the myriad of transcripts which continuously emerge vanish rapidly, some attain regulatory regions, become translated and survive. More surprisingly, sequence properties of de novo proteins are almost indistinguishable from randomly obtained sequences, yet de novo proteins may gain functions and integrate into eukaryotic cellular networks quite easily. We here discuss current knowledge on de novo proteins, their structures, functions and evolution. Since the existence of de novo proteins seems at odds with decade-long attempts to construct proteins with novel structures and functions from scratch, we suggest that a better understanding of de novo protein evolution may fuel new strategies for protein design.

• MeSH
• genomika MeSH
• molekulární evoluce * MeSH
• proteiny * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• proteiny * MeSH

Nineteen species of various families of the order Diptera and one species from the order Mecoptera are investigated with mass spectrometry for the presence and primary structure of putative adipokinetic hormones (AKHs). Additionally, the peptide structure of putative AKHs in other Diptera are deduced from data mining of publicly available genomic or transcriptomic data. The study aims to demonstrate the structural biodiversity of AKHs in this insect order and also possible evolutionary trends. Sequence analysis of AKHs is achieved by liquid chromatography coupled to mass spectrometry. The corpora cardiaca of almost all dipteran species contain AKH octapeptides, a decapeptide is an exception found only in one species. In general, the dipteran AKHs are order-specific- they are not found in any other insect order with two exceptions only. Four novel AKHs are revealed by mass spectrometry: two in the basal infraorder of Tipulomorpha and two in the brachyceran family Syrphidae. Data mining revealed another four novel AKHs: one in various species of the infraorder Culicumorpha, one in the brachyceran superfamily Asiloidea, one in the family Diopsidae and in a Drosophilidae species, and the last of the novel AKHs is found in yet another Drosophila. In general, there is quite a biodiversity in the lower Diptera, whereas the majority of the cyclorraphan Brachycera produce the octapeptide Phote-HrTH. A hypothetical molecular peptide evolution of dipteran AKHs is suggested to start with an ancestral AKH, such as Glomo-AKH, from which all other AKHs in Diptera to date can evolve via point mutation of one of the base triplets, with one exception.

• Klíčová slova
• adipokinetic and hypertrahalosemic biological assays, adipokinetic peptides, diptera, fly phylogeny, mass spectrometry,
• MeSH
• chromatografie kapalinová MeSH
• Diptera chemie   klasifikace   genetika   metabolismus   MeSH
• hmotnostní spektrometrie MeSH
• hmyzí hormony analýza   chemie   genetika   metabolismus   MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   analýza   chemie   metabolismus   MeSH
• molekulární evoluce * MeSH
• oligopeptidy analýza   chemie   genetika   metabolismus   MeSH
• peptidy analýza   chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokinetic hormone MeSH Prohlížeč
• hmyzí hormony MeSH
• kyselina pyrrolidonkarboxylová MeSH
• oligopeptidy MeSH
• peptidy MeSH

We have prepared organic guest molecules in which two pyridinium rings are connected through an aromatic/aliphatic bridge bearing a carboxyl group. The supramolecular interactions between these guests and macrocyclic hosts cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) has been studied. We have demonstrated that the binding modes of the complexes depend on the type of central bridge present in the guest molecules and the size of the macrocycle. We have also showed that the binding mode between cucurbiturils and guests with aromatic bridges is pH independent. On the other hand, a guest containing an aliphatic bridge and CB7 formed a pseudorotaxane, which behaved as a pH-driven molecular switch.

• MeSH
• imidazoly chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• makromolekulární látky chemická syntéza   chemie   MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• oxid uhličitý chemie   MeSH
• přemostěné cyklické sloučeniny chemie   MeSH
• rotaxany chemická syntéza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• carboxyl radical MeSH Prohlížeč
• cucurbit(7)uril MeSH Prohlížeč
• cucurbit(8)uril MeSH Prohlížeč
• imidazoly MeSH
• makromolekulární látky MeSH
• oxid uhličitý MeSH
• přemostěné cyklické sloučeniny MeSH
• rotaxany MeSH

This Special Issue of International Journal of Molecular Sciences (IJMS) contains 7 reviews and 12 original research papers written by a panel of experts who highlight recent advances in molecular structure and cellular function of purinergic P2 receptors[...].

• MeSH
• lidé MeSH
• purinergní receptory P2 chemie   metabolismus   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• úvodníky MeSH
• Názvy látek
• purinergní receptory P2 MeSH

The structure of the nonclassical pi kappa base pair (7-methyl-oxoformycin B. . .2,4-diaminopyrimidine) was studied at the ab initio Hartree-Fock (HF) and MP2 levels using the 6-31G* and 6-31G** basis sets. The pi kappa base pair is bound by three parallel hydrogen bonds with the donor-acceptor-donor recognition pattern. Recently, these bases were proposed as an extension of the genetic alphabet from four to six letters (Piccirilli et al, Nature 343,33 (1990)). By the HF/6-31G* method with full geometry optimization we calculated the 12 degree propeller twist for the minimum energy structure of this complex. The linearity of hydrogen bonds is preserved in the twisted structure by virtue of the pyramidal arrangement of the kappa-base amino groups. The rings of both the pi and kappa molecules remain nearly planar. This nonplanar structure of the pi kappa base pair is only 0.1 kcal/mol more stable than the planar (Cs) conformation. The HF/6-31G* level gas-phase interaction energy of pi kappa (-13.5 kcal/mol) calculated by us turned out to be nearly the same as the interaction energy obtained previously for the adenine-thymine base pair (-13.4 kcal/mol) at the same computational level. The inclusion of p-polarization functions on hydrogens, electron correlation effects (MP2/6-31G** level), and the correction for the basis set superposition error (BSSE) increase this energy to -14.0 kcal/mol.

• MeSH
• DNA chemie   MeSH
• formyciny chemie   MeSH
• konformace nukleové kyseliny * MeSH
• molekulární struktura MeSH
• pyrimidiny chemie   MeSH
• termodynamika MeSH
• vodíková vazba MeSH
• zastoupení bazí MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• 2,4-diaminopyrimidine MeSH Prohlížeč
• DNA MeSH
• formyciny MeSH
• oxoformycin B MeSH Prohlížeč
• pyrimidiny MeSH