Sequence variant (CTAGGG)n in the human telomere favors a G-quadruplex structure containing a G·C·G·C tetrad

Short contiguous arrays of variant CTAGGG repeats in the human telomere are unstable in the male germline and somatic cells, suggesting formation of unusual structures by this repeat type. Here, we report on the structure of an intramolecular G-quadruplex formed by DNA sequences containing four human telomeric variant CTAGGG repeats in potassium solution. Our results reveal a new robust antiparallel G-quadruplex fold involving two G-tetrads sandwiched between a G·C base pair and a G·C·G·C tetrad, which could represent a new platform for drug design targeted to human telomeric DNA.     

Insights into the strength and nature of carbene···halogen bond interactions: a theoretical perspective

Halogen-bonding, a noncovalent interaction between a halogen atom X in one molecule and a negative site in another, plays critical roles in fields as diverse as molecular biology, drug design and material engineering. In this work, we have examined the strength and origin of halogen bonds between carbene CH₂ and XCCY molecules, where X?=?Cl, Br, I, and Y?=?H, F, COF, COOH, CF₃, NO₂, CN, NH₂, CH₃, OH. These calculations have been carried out using M06-2X, MP2 and CCSD(T) methods, through analyses of surface electrostatic potentials V _S(r) and intermolecular interaction energies. Not surprisingly, the strength of the halogen bonds in the CH₂···XCCY complexes depend on the polarizability of the halogen X and the electron-withdrawing power of the Y group. It is revealed that for a given carbene···X interaction, the electrostatic term is slightly larger (i.e., more negative) than the dispersion term. Comparing the data for the chlorine, bromine and iodine substituted CH₂···XCCY systems, it can be seen that both the polarization and dispersion components of the interaction energy increase with increasing halogen size. One can see that increasing the size and positive nature of a halogen’s σ-hole markedly enhances the electrostatic contribution of the halogen-bonding interaction.

Detection of a 16S rRNA · initiator-tRNA complex by a new selective labelling method

Cupric-ion induced hydrolysis of [³⁵S]Met-tRNA but not of N-formyl-Met-tRNA _inff ^supMet permitted the specific terminal labelling of initiator tRNA. Initiator tRNA, labeled in this way, was suitable for sequence analysis without the need for further purification. By probing labeled initiator tRNA with specific RNases, changes in this molecule during its interaction with the 30S particle or with 16S rRNA were investigated. Initiation complexes were resistant to the action of single-strand, base-specific nucleases Bc and Phy M and, except for one base of the anticodon stem, were also resistant to digestion by the double-strand-specific V₁ nuclease of Naja venom. In contrast, T₁ RNase digestion of the initiator tRNA in the presence of 16S rRNA enhanced cleavage of bases in the T stem of the molecule.     

Sequence-dependent conformational heterogeneity of a hybrid DNA·RNA dodecamer duplex

Summary Two- and three-dimensional homonuclear NMR studies of a hybrid duplex RI, formed by annealing r(GCGCAAAACGCG) and d(CGCGTTTTGCGC) strands are described. NMR parameters, such as intra-and interresidue proton-proton NOEs and sugar proton coupling constants were analyzed with reference to those of the corresponding DNA·DNA duplex. Furthermore, spectral analyses were conducted on the basis of model structures of nucleic acid duplexes. Distinctive spectral patterns of the hybrid duplex reveal unique heterogeneous conformations which co-exist throughtout the sequence and are significantly different from those of model structures of either canonical A- or B-forms. Features of an intermediate conformation were observed in the DNA and RNA strands in duplex RI, the former being more B-like and the latter more A-like. Three-dimensional NOESY-NOESY spectra were analyzed and their use was demonstrated for resolving superimposed resonances and cross peaks, especially those originating from the RNA strand. The application of a useful strategy that combines the use of 2D NMR data and the known structural information for efficient 3D spectral analyses is demonstrated.     

Competition and interplay between the lithium bonding and hydrogen bonding: R3C···HY···LiY and R3C···LiY···HY triads as a working model (R=H, CH3; Y=CN, NC)

UMP2 calculations with aug-cc-pVDZ basis set were used to analyze intermolecular interactions in R₃C···HY···LiY and R₃C···LiY···HY triads (R=H, CH₃; Y=CN, NC), which are connected via lithium and hydrogen bonds. To better understand the properties of these systems, the corresponding dyads were also studied. Molecular geometries and binding energies of dyads, and triads were investigated at the UMP2/aug-cc-pVDZ computational level. Particular attention was paid to parameters such as cooperative energies, and many-body interaction energies. All studied complexes, with the simultaneous presence of a lithium bond and a hydrogen bond, showed cooperativity with energy values ranging between ?1.71 and ?9.03 kJ mol^?1. The electronic properties of the complexes were analyzed using parameters derived from atoms in molecules (AIM) methodology. Energy decomposition analysis revealed that the electrostatic interactions are the major source of the attraction in the title complexes.     

Rational redesign of a cation···π···π stacking at cardiovascular Fbw7–Skp1 complex interface and its application for deriving self-inhibitory peptides to disrupt the complex interaction

The Fbw7–Skp1 complex is an essential component in the formation and development of the mammalian cardiovascular system; the complex interaction is mediated through binding of Skp1 C-terminal peptide (qGlu-peptide) to the F-box domain of Fbw7. By visually examining the crystal structure, we identified a typical cation ···π···π stacking system at the complex interface, which is formed by the Trp1159 residue of qGlu-peptide with the Lys2299 and His2359 residues of Fbw7 F-box domain. Both hybrid quantum mechanics/molecular mechanics (QM/MM) analysis of the real domain–peptide complex and electron-correlation ab initio calculation of the stacking system model suggested that the cation···π···π plays an important role in stabilizing the complex; substitution of peptide Trp1159 residue with aromatic Phe and Tyr would not cause a considerable effect on the configuration and energetics of cation···π···π stacking system, whereas His substitution seems to largely destabilize the system. Subsequently, the qGlu-peptide was stripped from the full-length Skp1 protein to define a so-called self-inhibitory peptide, which may rebind to the domain–peptide complex interface and thus disrupt the complex interaction. Fluorescence polarization (FP) assays revealed that the Trp1159Phe and Trp1159Tyr variants have a comparable or higher affinity (K _d = 41 and 62 μM) than the wild-type qGlu-peptide (K _d = 56 μM), while the Trp1159His mutation would largely impair the binding potency of qGlu-peptide to Fbw7 F-box domain (K _d = 280 μM), confirming that the cation···π···π confers both affinity and specificity to the domain–peptide recognition, which can be reshaped by rational molecular design of the nonbonded interaction system.

Open image in new window

Graphical abstract Stereoview of the complex structure of Fbw7 with Skp1 (PDB: 2ovp), where the Trp1159 residue of Skp1 qGlu-peptide can form a cation···π···π stacking system with the Lys2299 and His2359 residues of Fbw7 F-box domain.

     

The electronic structure of the C2H4O···2HF tri-molecular heterocyclic hydrogen-bonded complex: a theoretical study

The geometries of three isomers of the C₂H₄O···2HF tri-molecular heterocyclic hydrogen-bonded complex were examined through B3LYP/aug-cc-pVDZ calculations. Analysis of structural parameters, determination of CHELPG (charge electrostatic potential grid) intermolecular charge transfer, interpretation of infrared stretching modes, and Bader’s atoms in molecules (AIM) theory calculations was carried out in order to characterize the hydrogen bonds in each isomer of the C₂H₄O···2HF complex. The most stable structure was determined through the identification of hydrogen bonds between C₂H₄O and HF, (O···H), as well as in the hydrofluoric acid dimer, (HF^D–R···HF^D). However, the existence of a tertiary interaction (F^λ···H^α) between the fluoride of the second hydrofluoric acid and the axial hydrogen atoms of C₂H₄O was decisive in the identification of the preferred configuration of the C₂H₄O···2HF system. Figure Geometries of three isomers of the C₂H₄O···2HF tri-molecular heterocyclic hydrogen-bonded complex     

Roles of electrostatic interaction and dispersion in CH···CH,CH···π, and π···π ethylene dimers

The structural, mechanical, electronic, and optical properties of orthorhombic Bi₂S₃ and Bi₂Se₃ compounds have been investigated by means of first principles calculations. The calculated lattice parameters and internal coordinates are in very good agreement with the experimental findings. The elastic constants are obtained, then the secondary results such as bulk modulus, shear modulus, Young’s modulus, Poisson’s ratio, anisotropy factor, and Debye temperature of polycrystalline aggregates are derived, and the relevant mechanical properties are also discussed. Furthermore, the band structures and optical properties such as real and imaginary parts of dielectric functions, energy-loss function, the effective number of valance electrons, and the effective optical dielectric constant have been computed. We also calculated some nonlinearities for Bi₂S₃ and Bi₂Se₃ (tensors of elasto-optical coefficients) under pressure.

问·题·解·答

问:假根与真根有什么区别?答:假根,一般为低等植物所特有,是具有吸收和固着作用的丝状结构,分枝或不分枝,仅由伸长的单细胞或单列的多细胞所构成,无组织分化。如藻类、真菌就具有这种假根。但是现存的高等植物中,苔藓植物以及蕨类植物的原叶体上也具有假根。真根较之于假根,主要在于有机械、输导等组织的分化。真根植物可以说是由仅有假根的无根类型逐渐进化而来的。一般来说,蕨类的孢子体世代以及种子植物都具有。不过,在某些如水生或腐生的种子植物中,由于其生存环境的特殊性,     

自学·质疑·精讲·练习

自学·质疑·精讲·练习”课堂教学方法,简易可行,便于推广,适宜不同年级、不同教学内容,便于穿插演示实验、讲解法等其他教学方法,使学生的主体作用、教师的主导作用得以充分发挥,有利于增强学生的集体主义精神,有利于培养学生的自学能力,提高分析问题、解决问题...     

·科研快讯·

《科学-转化医学》:按摩或可加速受损肌肉康复按摩疗法近年来被越来越多的人所接受。一项新研究也显示,按摩疗法可通过与大多数镇痛药相同的生物学机制来减轻肌肉疼痛,可能有助于受损肌肉     

Effect of stepwise microhydration on the methylammonium···phenol and ammonium···phenol interaction

A computational study has been performed for studying the characteristics of the interaction of phenol with ammonium and methylammonium cations. The effect of the presence of water molecules has also been considered by microhydrating the clusters with up to three water molecules. Clusters of phenol with ammonium and methylammonium cations present similar characteristics, though ammonium complexes have been found to be more stable than the methylammonium ones. The first water molecule included in the complexes interacts with a N-H group of ammoniun cations and simultaneously with the hydroxyl oxygen atom of phenol (or the aromatic ring). This first water molecule is more tightly bound in the complex, so the stability gain as more water molecules are included drops significantly by 2-3 kcal?mol^?1 with respect to the first one. As more water molecules are included, the differences between favorable coordination sites (the cation, the hydroxyl group or a previous water molecule) decrease. As a consequence, several of the most stable complexes located including three water molecules already exhibit hydrogen bonds between the hydroxyl group and one water molecule. The results indicate that a cyclic pattern formed by a series of hydrogen bonds: π···H-N-H···O-H···O-?, is characteristic of the most stable minima, being kept as more water molecules are included in the system. Therefore, this pattern can be expected to be crucial in ammonium cations···phenol interaction if exposed to the solvent to any degree.     

爱鸟·观鸟·赏鸟·护鸟

<正>"春眠不觉晓,处处闻啼鸟",唐代诗人孟浩然的诗句是我们儿时便能诵读的。春天代表着希望,鸟类寓意着新生。在这样一个春光明媚的时刻,我们怎能忘怀"自在娇莺恰恰啼"的美丽画卷呢?说到鸟类,我们总有无限的美好遐思——它们自由奔放,翱翔长空。它们婀娜多姿,步态轻盈。它们歌喉动听,嘤嘤啼啭……鸟类是自     

Identification of a Peptide Inhibitor of the RPM-1·FSN-1 Ubiquitin Ligase Complex

The Pam/Highwire/RPM-1 (PHR) proteins include: Caenorhabditis elegans RPM-1 (Regulator of Presynaptic Morphology 1), Drosophila Highwire, and murine Phr1. These important regulators of neuronal development function in synapse formation, axon guidance, and axon termination. In mature neurons the PHR proteins also regulate axon degeneration and regeneration. PHR proteins function, in part, through an ubiquitin ligase complex that includes the F-box protein FSN-1 in C. elegans and Fbxo45 in mammals. At present, the structure-function relationships that govern formation of this complex are poorly understood. We cloned 9 individual domains that compose the entire RPM-1 protein sequence and found a single domain centrally located in RPM-1 that is sufficient for binding to FSN-1. Deletion analysis further refined FSN-1 binding to a conserved 97-amino acid region of RPM-1. Mutagenesis identified several conserved motifs and individual amino acids that mediate this interaction. Transgenic overexpression of this recombinant peptide, which we refer to as the RPM-1·FSN-1 complex inhibitory peptide (RIP), yields similar phenotypes and enhancer effects to loss of function in fsn-1. Defects caused by transgenic RIP were suppressed by loss of function in the dlk-1 MAP3K and were alleviated by point mutations that reduce binding to FSN-1. These findings suggest that RIP specifically inhibits the interaction between RPM-1 and FSN-1 in vivo, thereby blocking formation of a functional ubiquitin ligase complex. Our results are consistent with the FSN-1 binding domain of RPM-1 recruiting FSN-1 and a target protein, such as DLK-1, whereas the RING-H2 domain of RPM-1 ubiquitinates the target.     

读者·作者·审者·编者

《中国生物化学与分子生物学报》自2006年1月起改为月刊为缩短出版周期,提高期刊学术水平和刊印质量,经《中国生物化学与分子生物学报》编委会讨论决定,上报中国生物化学与分子生物学会同意,获得中国科协和北京市新闻出版局批准,本刊自2006年1月起改为月刊,每月20日出版.每期96