Defining the minimal interacting regions of the tight junction protein MAGI-1 and HPV16 E6 oncoprotein for solution structure studies

The oncoprotein E6 produced by tumorigenic high-risk genital human papillomaviruses targets a number of cellular proteins containing PDZ domains for proteasome-mediated degradation. In particular, E6 targets the tight junction protein MAGI-1 by binding to its PDZ1 domain. Using light scattering and NMR, we explored different fragments of both the HPV16 E6 and the MAGI-1 PDZ1 domain to define the best-behaving complex for solution structure studies. We showed that the 70-residue HPV16 E6 C-terminal domain (E6C) can be efficiently substituted by a peptide spanning the 11 C-terminal residues of E6. The construct of MAGI-1 PDZ1 best suited for solution structure analysis presents a 14-residue N-terminal extension and a 26-residue C-terminal extension as compared to the construct used for the recently solved X-ray structure of a MAGI-1 PDZ1/HPV18 E6 complex. These data suggest a stabilizing role for the interdomain linker regions which separate the PDZ1 domain from its neighboring domains.     

生态系统中相互作用的激波问题

通过文[3,4,5]研究一类非线性发展系统在给出相应系统的初值能量的基础上,结合文[1,2]及[7]种群生态学、相应的生态环境和意义,讨论一类双曲型波方程的初边值问题,应用文[6]、[8]得到了其整体解在有限的相应作用过程中的破裂性.     

Structure-based differences between the metal ion selectivity of two siderophores desferrioxamine B (DFB) and desferricoprogen (DFC): why DFC is much better Pb(II) sequestering agent than DFB?

Complexation of desferrioxamine B (DFB) and desferricoprogen (DFC) with Cd(II) and Pb(II) toxic ions as well as complexation of DFC with Ca(II) and Mg(II) essential metals have been investigated and the results have been compared to those with other metal ions. The two siderophores have moderate Cd(II)-binding ability, but both, and especially DFC, bind Pb(II) in high stability complexes. Surprisingly, significant differences exist between Pb(II)-complexation of DFB and DFC. Namely, a maximum of two hydroxamate groups of a DFB coordinate to a Pb(II) ion, the third one binds to another metal ion with high preference and the formation of a trinuclear species, [Pb₃(DFBH)₂]²⁺, is predominant even at 1:1 metal to ligand ratio in this system. On the contrary, DFC forms mononuclear complex, [ML], with much higher stability and the formation of the trinuclear complex is negligible compared to DFB. The 6s² electron-pair of Pb(II), which remains always inert during complexation with hydroxamic acids and also with DFB, seems to become active in the DFC complexes (due to the effect of the double bonds in β-position to each hydroxamate), what, at least in some extent, allows the coordination of all the three hydroxamates of DFC to the same Pb(II) ion. This way of interaction (unique with a hydroxamate-based compound) results in significant stability increase, and, as a consequence, DFC is much better Pb(II)-chelating agent than DFB. Although DFC forms unexpectedly high stability complexes with Mg(II) compared to Ca(II), but even Mg(II), compared to many other metals, is not an efficient DFC-binding metal. Therefore, any sequestration of this biologically very important metal is not likely from a living organism by DFC.     

Replacement of the methionine axial ligand in cytochrome c550 by a lysine: effects on the haem electronic structure

The prosthetic group of low-spin haem proteins is an iron porphyrin with two axial ligands, typically histidine, methionine or lysine. Determining the geometry of the axial ligands is an important step in structural characterisation, particularly in the paramagnetic oxidised forms. This work extends earlier studies of the hyperfine nuclear magnetic resonance (NMR) shifts of haem substituents in bis-His and His–Met cytochromes to His–Lys co-ordination in the M100K mutant of Paracoccus versutus cytochrome c₅₅₀. The electronic structure of the His–Lys haem is shown to be similar to that produced by His–cyanide co-ordination, such that NMR can be used to determine the geometry of the His ligand.     

Homopolynuclear and heteropolynuclear Rh(III) aqua ions - a review

The kinetic inertness of Rh(III) has facilitated investigations of the early stages of hydrolytic polymerization of [Rh(OH₂)₆]³⁺. These studies have led to the synthesis, solution characterization and determination of the X-ray crystal structure of a series of polynuclear aqua ions, which range in nuclearity from binuclear to tetranuclear. The inertness of Rh(III) has enabled the identification of three structural forms of the trinuclear aqua ion which vary in their degree of condensation as well as detailed kinetic and mechanistic studies of water exchange on the binuclear aqua ion, [Rh₂(μ-OH)₂(OH₂)₈]⁴⁺, applying both ¹⁸O isotopic labeling and ¹⁷O NMR spectroscopy. Strategies have been developed which led to the quite efficient synthesis of heteropolynuclear Rh(III)-Cr(III) aqua ions and a heterobinuclear Rh(III)-Ir(III) aqua ion. Elucidation of the composition, properties and structure of heteropolynuclear aqua ions has been possible by applying techniques that had been instrumental in the development of the chemistry of homometallic aqua ions. Kinetic and thermodynamic studies of the Rh(III)-Cr(III) aqua ions generally revealed thermodynamic and activation parameters that corresponded to those for similar processes occurring at Cr(III), as may have been expected given the greater lability of Cr(III) relative to Rh(III). Inductive effects caused by the Rh(III) centers do, however, influence reactivity as exemplified by the slower than expected rate of cleavage of [CrRh₂(μ-OH)₄(OH₂)₁₀]⁵⁺.     

大数据时代的整合生物信息学

随着生物数据测量技术的不断发展,生物数据的类型、内容、复杂度不断增加,生物信息学已迈入大数据时代。面对大数据时代多模态、多层次、高维度、非线性的复杂生物数据,生物信息学需要发展相应的方法和技术进行有效整合生物信息学研究与应用。本文对大数据时代整合生物信息学所涉及的数据整合、方法整合、系统整合及相关问题进行梳理和探讨。     

食饵具有周期强迫的捕食模型

建立并研究了一类具有周期强迫和脉冲扰动的捕食模型,通过理论分析和数值模拟,得到了食饵灭绝周期解全局渐近稳定和系统持久的充分条件,利用分支理论证明了边界周期解附近会分支出正周期解.     

Interactions of insulin-mimetic zinc(II) complexes with cell constituents: glutathione and ATP

Ternary complex formation of some potent insulin-mimetic zinc(II) complexes of bidentate ligands: maltol and 3-hydroxy-1,2-dimethyl-pyridinone with (O,O), 2-picolinic acid and 6-methylpicolinic acid with (N,O) and the tridentate 2,6-dipicolinic acid with (O,N,O) coordination modes was studied in aqueous solutions by pH-potentiometry and spectroscopic (UV, CD, ESI-MS) methods in the presence of critical cell constituents such as l-glutathione reduced (GSH) and adenosine 5′-triphosphate (ATP). Results showed that formation of the ternary complexes was hindered in the case of 2,6-dipicolinic acid, especially with ATP, while it was favoured with the bidentate ligands in the physiological pH range. Driving force of the formation of mixed-ligand species was found to be a more enhanced coordination of GSH and ATP as second ligands in the ternary complexes than in their binary ones due to steric and electrostatic reasons. The mitochondrial dehydrogenase activity of the zinc(II) complexes, as an indirect indicator for the glucose intake, was measured on Mono Mac and 3T3-L1 adipocyte cell lines. The activity of the complexes up to ∼10-100 μM concentration was in the range of the effect of 0.75-1.5 μM insulin, while at higher concentration it was broken down due to the sensitivity of the cells to toxicity of the complexes.     

电渗析技术用于猪毛水解液脱酸的研究

利用上海华凯科技贸易公司制作的HF系列离子交换膜为隔膜的电渗析器对猪毛水解液进行电渗析脱酸,研究了脱酸过程中浓缩室、淡化室酸度变化及电流效率