Zinc binding to peptide analogs of the structural zinc site in alcohol dehydrogenase: Implications for an entatic state

Zinc binding to the peptide replica and analogs to residues 93–115 of horse liver alcohol dehydrogenase (ADH) was examined by competition of the peptides and the chromophoric chelator 4-(2- pyridylazo)resorcinol for zinc and X-ray absorption fine structure analysis of the zinc ligands. In the enzyme, zinc is coordinated by four Cys residues. In the peptide replica, zinc is bound to three Cys and one His residue. A four-Cys zinc coordination is observed only when His is removed, leading to increased zinc stability. ADH crystal structures reveal that the ε-amino group of the conserved residue Lys323 is within H-bond distance of the backbone amide oxygens of residues 103, 105 and 108, likely stabilizing the zinc coordination in the enzyme. The peptide data thus indicate structural strain and increased energy in the zinc-binding site in the protein, characteristic of an entatic state, implying a functional nature for this zinc site. Received 3 July 2008; received after revision 11 August 2008; accepted 1 September 2008     

On the mechanism of inhibition of p27 degradation by 15-deoxy-Δ12,14-prostaglandin J 2 in lymphoblasts of Alzheimer’s disease patients

It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients. We previously reported that the anti-inflammatory 15- deoxy-Δ^12,14-prostaglandin J ₂ (15d-PGJ ₂) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work aimed at elucidating the mechanisms of 15d-PGJ ₂-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2 by mechanisms dependent on PI3K/Akt activity. 15d-PGJ ₂ prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory subunit of PI3K. These effects of 15d-PGJ ₂ were not mimicked by 9,10-dihydro-15-deoxy-Δ^12,14- prostaglandin J ₂, suggesting that 15d-PGJ ₂ acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group in the cyclopentenone ring of 15d-PGJ ₂ is a requisite for the observed effects. Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008     

SEA方法及其在$C^3I$系统效能分析中的应用(Ⅲ)——监视模型

针对ＳＥＡ方法的要求,提出了评估$Ｃ^３Ｉ$系统在执行监视任务时的系统效能的三个性能量度（ＭＯＰ）,通过分析$Ｃ^３Ｉ$系统在执行监视任务时的行为过程和环境特点,结合排队理论,建立了评估$Ｃ^３Ｉ$系统监视效能的ＳＥＡ方法模型．利用该模型计算了一个实际$Ｃ^３Ｉ$系统的监视效能,并对结果进行了简要分析．     

CCD精密测量系统及其数字信号处理

介绍了ＣＣＤ精密测量系统中的信号采集和处理的工作原理,阐述了测量系统和数字信号处理芯片（ＤＳＰ芯片）在系统中的工作原理,同时还介绍了测量系统的软件工作过程。文中概要介绍了ＣＣＤ器件的工作原理和ＣＣＤ器件用于测量中的特点。通过本文,我们可以了解到ＣＣＤ精密测量系统中ＤＳＰ芯片的作用。     

Ba2ErCl7晶体的生长、结构和激光上转换机制

报道了新型上转换材料Ｂａ２ＥｒＣｌ７的单晶生长方法。用“一步合成法”直接将Ｅｒ２Ｏ３,ＢａＣｌ２．２Ｈ２Ｏ和ＮＨ４Ｃｌ合成Ｂａ２ＥｒＣｌ７多晶料,并分别用提拉法和坩埚下降法得到４ｍｍ＊８ｍｍ＊１５ｍｍ的优质大块单晶;用８０３ｎｍ的ＬＤ泵浦时有强烈的黄绿光发射;     

低码率下MPEG—2自适应量化控制策略

对ＭＰＥＧ－２ＴＭ５量化控制策略进行了修正,提出了一种基于宏块直方图特性的自适应量化控制方法．该方法考虑了人眼的视觉特性和编码效率,适应于低码率下的ＭＰＥＧ－２压缩编码,并能有效地提高图象质量．     

Cancer and blood coagulation

In human patients, blood coagulation disorders often associate with cancer, even in its early stages. Recently, in vitro and in vivo experimental models have shown that oncogene expression, or inactivation of tumour suppressor genes, upregulate genes that control blood coagulation. These studies suggest that activation of blood clotting, leading to peritumoral fibrin deposition, is instrumental in cancer development. Fibrin can indeed build up a provisional matrix, supporting the invasive growth of neoplastic tissues and blood vessels. Interference with blood coagulation can thus be considered as part of a multifaceted therapeutic approach to cancer. Received 30 November 2005; received after revision 7 February 2005; accepted 8 February 2006     

Recent results on hydrogen and hydration in biology studied by neutron macromolecular crystallography

Neutron diffraction provides an experimental method of directly locating hydrogen atoms in proteins, a technique complimentary to ultra-high-resolution [1, 2] X-ray diffraction. Three different types of neutron diffractometers for biological macromolecules have been constructed in Japan, France and the United States, and they have been used to determine the crystal structures of proteins up to resolution limits of 1.5-2.5 A. Results relating to hydrogen positions and hydration patterns in proteins have been obtained from these studies. Examples include the geometrical details of hydrogen bonds, H/D exchange in proteins and oligonucleotides, the role of hydrogen atoms in enzymatic activity and thermostability, and the dynamical behavior of hydration structures, all of which have been extracted from these structural results and reviewed. Other techniques, such as the growth of large single crystals, the preparation of fully deuterated proteins, the use of cryogenic techniques, and a data base of hydrogen and hydration in proteins, will be described.     

Family I.3 lipase: bacterial lipases secreted by the type I secretion system

Based on the classification of bacterial lipolytic enzymes, family I.3 lipase is a member of the large group of Gram-negative bacterial true lipases. This lipase family is distinguished from other families not only by the amino acid sequence, but also by the secretion mechanism. Lipases of family I.3 are secreted via the well-known type I secretion system. Like most of proteins secreted via this system, family I.3 lipases are composed of two domains with distinct yet related functions. Recent years have seen an increasing amount of research on this lipase family, in terms of isolation, secretion mechanism, as well as biochemical and biophysical studies. This review describes our current knowledge on the structure-function relationships of family I.3 lipase, with an emphasis on its secretion mechanism. Received 18 April 2006; received after revision 3 July 2006; accepted 24 August 2006     

Optimization of the cellular import of functionally active SH2-domain-interacting phosphopeptides

Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into B cells. We found octanoyl-Arg₈ to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and time-dependent manner. Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006