Structure of the δ-opioid receptor bound to naltrindole

The opioid receptor family comprises three members, the μ-, δ- and κ-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The δ-opioid receptor (δ-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the μ-OR and κ-OR have recently been solved. Here we report the crystal structure of the mouse δ-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the μ-OR and κ-OR, the δ-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the δ-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.     

Structure of the human κ-opioid receptor in complex with JDTic

Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and--in the case of κ-opioid receptor (κ-OR)--dysphoria and psychotomimesis. Here we report the crystal structure of the human κ-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9?? resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human κ-OR. Modelling of other important κ-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5'-guanidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure-activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for κ-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human κ-OR.     

Crystal structure of oxygen-evolving photosystem II at a resolution of 1.9 Å

Photosystem II is the site of photosynthetic water oxidation and contains 20 subunits with a total molecular mass of 350 kDa. The structure of photosystem II has been reported at resolutions from 3.8 to 2.9 ?. These resolutions have provided much information on the arrangement of protein subunits and cofactors but are insufficient to reveal the detailed structure of the catalytic centre of water splitting. Here we report the crystal structure of photosystem II at a resolution of 1.9 ?. From our electron density map, we located all of the metal atoms of the Mn(4)CaO(5) cluster, together with all of their ligands. We found that five oxygen atoms served as oxo bridges linking the five metal atoms, and that four water molecules were bound to the Mn(4)CaO(5) cluster; some of them may therefore serve as substrates for dioxygen formation. We identified more than 1,300 water molecules in each photosystem II monomer. Some of them formed extensive hydrogen-bonding networks that may serve as channels for protons, water or oxygen molecules. The determination of the high-resolution structure of photosystem II will allow us to analyse and understand its functions in great detail.     

Crystal structure of the β2 adrenergic receptor-Gs protein complex

G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 ? outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.     

Crystal structure of a concentrative nucleoside transporter from Vibrio cholerae at 2.4 Å

Nucleosides are required for DNA and RNA synthesis, and the nucleoside adenosine has a function in a variety of signalling processes. Transport of nucleosides across cell membranes provides the major source of nucleosides in many cell types and is also responsible for the termination of adenosine signalling. As a result of their hydrophilic nature, nucleosides require a specialized class of integral membrane proteins, known as nucleoside transporters (NTs), for specific transport across cell membranes. In addition to nucleosides, NTs are important determinants for the transport of nucleoside-derived drugs across cell membranes. A wide range of nucleoside-derived drugs, including anticancer drugs (such as Ara-C and gemcitabine) and antiviral drugs (such as zidovudine and ribavirin), have been shown to depend, at least in part, on NTs for transport across cell membranes. Concentrative nucleoside transporters, members of the solute carrier transporter superfamily SLC28, use an ion gradient in the active transport of both nucleosides and nucleoside-derived drugs against their chemical gradients. The structural basis for selective ion-coupled nucleoside transport by concentrative nucleoside transporters is unknown. Here we present the crystal structure of a concentrative nucleoside transporter from Vibrio cholerae in complex with uridine at 2.4??. Our functional data show that, like its human orthologues, the transporter uses a sodium-ion gradient for nucleoside transport. The structure reveals the overall architecture of this class of transporter, unravels the molecular determinants for nucleoside and sodium binding, and provides a framework for understanding the mechanism of nucleoside and nucleoside drug transport across cell membranes.     

Reexploring the upper bound for the chromatic number of graphs

The upper bound of the chromatic number of simple graphs is explored. Its original idea comes from Coffman, Hakimi and Schmeichel, who recently studied the chromatic number of graphs with strong conditions. In this paper, corresponding conditions are weakened and the result proves that of Ershov and Kozhukhin's.     

Refinement of the crystal structure for a new mineral──antimonselite

The crystal structure of a new mineral of the stibnite group, Sb-2Se-3, has been determined. The cell constants, obtained by least-squares calculation from direct θ -value's measurements on the diffractometer are: a =1.158 8(5), b =1.174 4(4), c =0.395 5(2) nm; orthorhombic; V =0.538 23 nm+3; Z =4. The space group is Pbnm. X-ray single crystal data, using Mo K α radiation, were measured on a RIGAKU RASA-5RP automated diffractometer and refined to a final R index of 0.048 1. Sb-2Se-3 is isostructural with Sb-2S-3 and Bi-2S-3. Each Sb(1) atom is six-coordinated by 3 Se(1), 1 Se(2) and 2 Se(3) atoms at distances 0.266 0-0.323 6 nm. Each Sb(2) atom is seven-coordinated by 2 Se(1), 2 Se(2) and 3 Se(3) atoms at distances of 0.258 1- 0.346 7 nm. The crystal structure consists of chains parallel to c or needle axis. The strongest bonds (shortest separations) are within the chains. Many important physical properties of antimonselite (optical, ferroelectric, etc.) are related to its crystal structure.     

Is the existence of a J/ψJ/ψ bound state plausible?

In a recent measurement LHCb reported pronounced structures in the J/ψJ/ψ spectrum.One of the var-ious possible explanations of those is that they emerge from n...     

Dynamic structure factor of a Bose-Hubbard gas

The dynamic structure factor of a Bose-Einstein condensate in an optical lattice, momentum and energy rates imparted to the condensate are analyzed in detail as the function of both the lattice depth and the strength of the two-body interaction. Our investigation shows that the lattice depth strongly affects the dynamic structure factor. An oscillating behavior of both the static structure factor and excitation strength as a function of the momentum transfer has been developed. We also show how interatomic interaction affects these processes and discuss the conditions for possible experimental realization.     

Crystal structure determining of 7-ADCA based on X-ray powder diffraction

Traditionally, crystal structure data can be collected and determined from single-crystal X-ray diffraction. However, in the fields of organic and macromolecular crystallography, it is often difficult or impractical to grow single crystals with suitable sizes and purity. Therefore, it will be benefited from the newly growing analytical tool that combining X-ray powder diffraction based on polycrystalline samples and ab initio calcula- tion[1]. 7-ADCA is one of the most important intermediate…     

The role of cupric in maintaining the structure of CopC

The CopC protein from pseudomonas syringae pathovar tomato is expressed as one of four proteins encoded by the operon CopABCD that is responsible for copper resistance. And there are one trypto-phan (83), one tyrosine (79), and three phenylalanines (35, 43, 99) in apoCopC. The fluorescence peak of apoCopC is located near 320 nm, and the peak shifts toward 353 nm in the presence of 10 mmol·L~(-1) urea with excitation at 280 nm. Using urea as a chemical agent, the conformational stabilities of apoCopC and Cu_N~(2 ) -CopC were monitored by fluorescence spectrum in 20 mmol·L~(-1) phosphate buffer and 100 mmol·L~(-1) sodium chloride at pH 6.0. The free energy of stabilization for apoCopC and Cu_N~(2 )-CopC is 16.29±0.65 kJ·mol~(-1) and 26.26±0.35 kJ·mol~(-1), respectively. The distance between the tryptophan residue and the Cu~(2 ) in Cu_N~(2 ) -CopC has been studied by observing Frster type nonradia-tive energy transfer. And it is calculated to be 11.6 .     

Crystal structure and surface photo-electric property of Mn（Ⅱ） coordination supramolecules

Two Mn（Ⅱ） coordination supramolecules, [Mn2（C8HTO2）4（phen）2（p-H20）] （1） and [Mn2（btec）（phen）2（H2O）6]·2H2O （2） （phen=1,10-phenanthroline, H4btec=1,2,4,5-benzenetetracarboxylic acid）, were synthesized by hydrothermal method. The crystal structures of the complexes were determined by X-ray single crystal diffraction. The result indicates that （1） and （2） are both binuclear Mn（Ⅱ） complexes. The existence of hydrogen bonds makes the binuclear complexes become further connected to coordination supramolecules, which possess 1D and 3D infinite structures respectively. The complexes were identified by IR, UV-Vis, surface photovoltage spectrum （SPS） and field-induced surface photovoltage spectrum （FISPS）. The results of SPS for the complexes indicate that they both exhibit positive surface photovoltage response bands in the range of 300-600 nm. The SPS phase spectrum and FISPS of complexes indicate that they show certain p-type semiconductor characteristic. However, the intensity, position and number of the SPV response bands are different obviously. The difference of the SPV response bands is mainly attributed to the different structures of the complexes and the different coordination environment of Mn（ll） in the two complexes. This paper discusses the action of hydrogen bonds in the construction of the supramolecule and the change on the surface photovoltage of complex in different coordination environment.     

A linear analysis of the space structure of the standard plot in city

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1,3-dioxolane pretreatment to improve the interfacial characteristics of a lithium anode

1,3-dioxolane pretreatment to improve the interfacial characteristics of a lithium anode     

Optimization for the structure of BF hearth bottom and the arrangement of thermal couples

The hearth of ＂heat transfer method＂ and the ceramic cup synthetic hearth bottom of ＂heart isolation method＂ are two most popular designs for blast furnace （BF）. Although there are successful real examples, some disadvantages, for instance large heat loss and high cost, still exist for these designs. According to the theory of heat transfer, based on the calculation of temperature distribution of the hearth bottom, it is elucidated that all brick layers at the hearth bottom may not be considered as the only reason why different structures exhibited different temperature distributions although total heat resistance is the same, and then based on the effect of hot metal and cold water on different temperature distribution ranges, the concepts of ＂heat resistance＂ and ＂cooling enhancement＂ are put forth. Based on this, the disadvantages and the factors affecting temperature distribution, of the two types of hearth bottoms were illustrated. On the basis of these analyses, a novel structure for BF hearth bottom designing that can easily form ＂self-protecting＂ slag layer stably, called ＂the method of gradient brick layout that has an optimum combination of cooling enhancement and heat resistance＂ was proposed; it can not only prolong the hearth bottom longevity but also reduce the cost and heat loss.     

Diagnostic analysis of the asymmetric structure of the simulated landfalling typhoon “Haitang”

The landfalling processes of Typhoon ＂Haitang＂ near Lianjiang of Fujian Province of China from 00 UTC 19 to 12 UTC 20 July 2005 were reproduced by using the nesting non-hydrostatic WRF model and data assimilation technology （Level II Doppler radar data of Changle of Fujian Province are assimilated to the simulation every one hour from 01 to 06 UTC 19 July 2005）. The mesoscale structure and evolution of the typhoon before, during, and after its landfall were discussed. The simulation data show that the assimilation exper- iment with the high temporal-and-spatial-resolution radar radial velocity and reflectivity data can produce much better simulation of the typhoon track, intensity evolution and landfalling location than the control experiment without assimilating radar data. By using the assimilation experimental data, the mesoscale fine-mesh structure and evolution before and after typhoon landfall were analyzed. Because of the influence of sea-land thermodynamic difference, two asymmetric convective regions were located at ocean and land, respectively. To better understand and investigate the asymmetric-structure characteristics of the landfalling typhoon, several dynamical diagnostic tools, the helicity （H）, the moist potential vorticity （MPV）, the convective vorticity vector （CVV）, the moist vorticity vector （MVV）, which are associated with the development of strong convections, are introduced. Further analysis illuminates that the distribu- tions of these physical diagnostic parameters are totally asymmetric, and subsequently, the associated convections also show distinct asymmetry.     

Study on the Technology of Restoration and Giving a New Lease of Life to the Alpine Grassland Vegetation in the Constuction of the Qinghai-Tibet Railway

1BasicBackgroundoftheExperi mentalStudy1.1TheBasisandPurposeoftheStudyTheconstructionoftheQinghai TibetRailwayistheensuranceoftheprosperityandsustainable developmentofQinghaiProvinceandTibetAutonomousRegion.Throughscientificandexperimentalstudyandtheapplicationofnew technology,strengtheningtheprotectionofecologicalenvironmentandtherestorationofthesurfacevegetationaftertheconstructionaretheimportantworkcontentofbuildingtheQinghai TibetRailwayintotherailwayofenvironmentalprotection.Ontheq…     

Study on the Technology of Restoration and Giving a New Lease of Life to the Alpine Grassland Vegetation in the Construction of the Qinghai-Tibet Railway

This article gives a summary and analasis to experimental study on the restoration and giving a new lease of life to the alpine grassland vegetation along the Qinghai-Tibet Railway. Through on-the-spot investigation and vegetaion storation experimental study to the constructive fetching soil ground in Tuotuo River experiment section in the construction of the Qinghai-Tibet Railway, the result shows ： after the activities of the construction, soil conditions on the fetching soil ground have changed a lot, the soil quality has obviously degraded. In order to do well the vegetaton storation and reconstruction in the process of the construction of the Qinghai-Tibet Railway, the backfilling of the surface soil should really be done well. According to the result of on -the-spot experiment, the Elymus dahuricus Turcz and Poa annua Linn are all more suitable to the fetching soil environment on the alpine grassland, the plant can normally grow in the growing season. The timing selection of the vegetation should fully use feature of both rain and heat in the same season, thus can improve the percentage of success.