Home About us Contact
|
Home About us Contact | ||
|
|
||
Functional Sites (functional + site)
Selected AbstractsPLACE, PRINT AND MIRACLE: FORLÍ'S MADONNA OF THE FIRE AS FUNCTIONAL SITEART HISTORY, Issue 3 2008LISA PON The Madonna of the Fire of Forlì is an early woodcut that miraculously survived a fire in 1428, and still resides in the cathedral of Forlì, a city southeast of Bologna. This miracle removed the woodcut from the traffic in images crossing geographic and chronological boundaries in which other early modern prints participated. Since 1428 it has acted instead as a functional site, bound to a single place and able to galvanize disparate local elements into a communal sense of emplacement. This essay explores both that ability to generate a local identity, as well as the Madonna of the Fire's status as a miraculous object. For the transformation of the Madonna of the Fire from quotidian devotional print to miraculous cult icon also activated its ability to work as a functional site by charging overlapping material, geographic and discursive loci with communal significance. [source] Coloration of monodispersed polystyrene nanoparticles prepared via the RAFT reactionPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 3 2006Ju Sung Kim Abstract Highly monodispersed polystyrene (PS) nanoparticles were prepared via the reversible addition fragmentation transfer (RAFT) living radical emulsion polymerization technique using a sur-iniferter, 4-(2-hydroxyethyl)piperazine-1-carbodithioicacid benzylether (HPCB). The monodispersed nanoparticles were colored by various methods, namely random and block copolymeriztion, the end group reaction and the adsorption method. For the coloration of the block and random copolymer monodispersed nanoparticles, a color pre-monomer was previously synthesized with a vinyl functional site. Dynamic light scattering and scanning electron microscopy were the main tools used to analyze the size and distribution of the prepared nanoparticles. Copyright © 2006 John Wiley & Sons, Ltd. [source] PLACE, PRINT AND MIRACLE: FORLÍ'S MADONNA OF THE FIRE AS FUNCTIONAL SITEART HISTORY, Issue 3 2008LISA PON The Madonna of the Fire of Forlì is an early woodcut that miraculously survived a fire in 1428, and still resides in the cathedral of Forlì, a city southeast of Bologna. This miracle removed the woodcut from the traffic in images crossing geographic and chronological boundaries in which other early modern prints participated. Since 1428 it has acted instead as a functional site, bound to a single place and able to galvanize disparate local elements into a communal sense of emplacement. This essay explores both that ability to generate a local identity, as well as the Madonna of the Fire's status as a miraculous object. For the transformation of the Madonna of the Fire from quotidian devotional print to miraculous cult icon also activated its ability to work as a functional site by charging overlapping material, geographic and discursive loci with communal significance. [source] Structure of the Calx-, domain of the integrin ,4 subunit: insights into function and cation-independent stabilityACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2009Noelia Alonso-García The integrin ,6,4 is a receptor for laminins and provides stable adhesion of epithelial cells to the basement membranes. In addition, ,6,4 is important for keratinocyte migration during wound healing and favours the invasion of carcinomas into surrounding tissue. The cytoplasmic domain of the ,4 subunit is responsible for most of the intracellular interactions of the integrin; it contains four fibronectin type III domains and a Calx-, motif. The crystal structure of the Calx-, domain of ,4 was determined to 1.48,Å resolution. The structure does not contain cations and biophysical data support the supposition that the Calx-, domain of ,4 does not bind calcium. Comparison of the Calx-, domain of ,4 with the calcium-binding domains of Na+/Ca2+ -exchanger 1 reveals that in ,4 Arg1003 occupies a position equivalent to that of the calcium ions in the Na+/Ca2+ -exchanger. By combining mutagenesis and thermally induced unfolding, it is shown that Arg1003 contributes to the stability of the Calx-, domain. The structure of the Calx-, domain is discussed in the context of the function and intracellular interactions of the integrin ,4 subunit and a putative functional site is proposed. [source] VSD: A database for schizophrenia candidate genes focusing on variations,HUMAN MUTATION, Issue 1 2004Min Zhou Abstract Schizophrenia is a common mental disease characterized by delusions, hallucinations, and formal thought disorder. It has been demonstrated with genetic evidence that the disease is a polygenic disorder. Pharmacological, neurochemical, and clinical studies have suggested a number of schizophrenia susceptibility loci. In order to systematically search for genes with small effect in the development of schizophrenia, a database called VSD was established to provide variation data for publicly available candidate genes. Most of the genes encode neurotransmitter receptors, neurotransmitter transporters, and the enzymes involved in their metabolism. Other candidate genes extracted from published literature are also included. The variation information has been collected from publicly available mutation and polymorphism databases such as dbSNP, HGVbase, and OMIM, with single nucleotide polymorphism (SNP) being the most abundant form of collected variations. Reference sequences from NCBI's RefSeq database are used as references when positioning variation at transcript and protein levels. The nonsynonymous SNPs (nsSNPs) that lead to amino acid changes in the functional sites or domains of proteins are distinguished since they are more likely to affect protein function and would be target SNPs for association studies. In addition to variation data, gene descriptions, enzyme information, and other biological information for each gene locus are also included. The latest version of VSD contains 23,648 variations assigned to a total of 186 genes. Five-hundred eighty-eight domains and sites annotated in the SWISS-PROT and InterPro databases are found to contain nsSNPs. VSD may be accessed via the World Wide Web (www.chgb.org.cn/vsd.htm) and will be developed as an up-to-date and comprehensive locus-specific resource for identifying susceptibility genes for schizophrenia. Hum Mutat 23:1,7, 2004. © 2003 Wiley-Liss, Inc. [source] Probing of Functionalized Mesoporous Silica Nanoparticles Using Transition Metal Clusters,ADVANCED MATERIALS, Issue 21 2003S. Hermans Molecular clusters (homo- and bi-metallic) have been used to gain structural information on nanoparticles of mesoporous silica (see Figure). Using scanning transmission electron microscopy, the spatial distribution of clusters has been imaged to determine the accessibility of the mesopores. The clusters are also used as "stains" to determine the exact location and number of functional sites within the substrates. [source] A quantitative strategy to detect changes in accessibility of protein regions to chemical modification on heterodimerizationPROTEIN SCIENCE, Issue 7 2009Mathias Dreger Abstract We describe a method for studying quantitative changes in accessibility of surface lysine residues of the PB1 subunit of the influenza RNA polymerase as a result of association with the PA subunit to form a PB1-PA heterodimer. Our method combines two established methods: (i) the chemical modification of surface lysine residues of native proteins by N -hydroxysuccinimidobiotin (NHS-biotin) and (ii) the stable isotope labeling of amino acids in cell culture (SILAC) followed by tryptic digestion and mass spectrometry. By linking the chemical modification with the SILAC methodology for the first time, we obtain quantitative data on chemical modification allowing subtle changes in accessibility to be described. Five regions in the PB1 monomer showed altered reactivity to NHS-biotin when compared with the [PB1-PA] heterodimer. Mutational analysis of residues in two such regions,at K265 and K481 of PB1, which were about three- and twofold, respectively, less accessible to biotinylation in the PB1-PA heterodimer compared with the PB1 monomer, demonstrated that both K265 and K481 were crucial for polymerase function. This novel assay of quantitative profiling of biotinylation patterns (Q-POP assay) highlights likely conformational changes at important functional sites, as observed here for PB1, and may provide information on protein,protein interaction interfaces. The Q-POP assay should be a generally applicable approach and may detect novel functional sites suitable for targeting by drugs. [source] Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acidPROTEIN SCIENCE, Issue 2 2008Freddie R. Salsbury Jr Abstract Cysteine sulfenic acid (Cys-SOH), a reversible modification, is a catalytic intermediate at enzyme active sites, a sensor for oxidative stress, a regulator of some transcription factors, and a redox-signaling intermediate. This post-translational modification is not random: specific features near the cysteine control its reactivity. To identify features responsible for the propensity of cysteines to be modified to sulfenic acid, a list of 47 proteins (containing 49 known Cys-SOH sites) was compiled. Modifiable cysteines are found in proteins from most structural classes and many functional classes, but have no propensity for any one type of protein secondary structure. To identify features affecting cysteine reactivity, these sites were analyzed using both functional site profiling and electrostatic analysis. Overall, the solvent exposure of modifiable cysteines is not different from the average cysteine. The combined sequence, structure, and electrostatic approaches reveal mechanistic determinants not obvious from overall sequence comparison, including: (1) pKas of some modifiable cysteines are affected by backbone features only; (2) charged residues are underrepresented in the structure near modifiable sites; (3) threonine and other polar residues can exert a large influence on the cysteine pKa; and (4) hydrogen bonding patterns are suggested to be important. This compilation of Cys-SOH modification sites and their features provides a quantitative assessment of previous observations and a basis for further analysis and prediction of these sites. Agreement with known experimental data indicates the utility of this combined approach for identifying mechanistic determinants at protein functional sites. [source] Synthesis and NMR solution structure of an ,-helical hairpin stapled with two disulfide bridgesPROTEIN SCIENCE, Issue 5 2000Philippe Barthe Abstract Helical coiled-coils and bundles are some of the most common structural motifs found in proteins. Design and synthesis of ,-helical motifs may provide interesting scaffolds that can be useful as host structures to display functional sites, thus allowing the engineering of novel functional miniproteins. We have synthesized a 38-amino acid peptide, ,2p8, encompassing the ,-helical hairpin present in the structure of p8MTCP1, as an ,-helical scaffold particularly promising for its stability and permissiveness of sequence mutations. The three-dimensional structure of this peptide has been solved using homonuclear two-dimensional NMR techniques at 600 MHz. After sequence specific assignment, a total of 285 distance and 29 dihedral restraints were collected. The solution structure of ,2p8 is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics, using simulated annealing protocol with the AMBER force field. The RMSD values for the backbone and all heavy atoms are 0.65 ± 0.25 and 1.51 ± 0.21 Å, respectively. Excised from its protein context, the ,-hairpin keeps its native structure: an ,-helical coiled-coil, similar to that found in superhelical structures, with two helices spanning residues 4-16 and 25,36, and linked by a short loop. This motif is stabilized by two interhelical disulfide bridges and several hydrophobic interactions at the helix interface, leaving most of its solvent-exposed surface available for mutation. This ,-helical hairpin, easily amenable to synthetic chemistry and biological expression system, may represent a stable and versatile scaffold to display new functional sites and peptide libraries. [source] Refined structures of placental alkaline phosphatase show a consistent pattern of interactions at the peripheral siteACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 8 2010Boguslaw Stec In order to gain deeper insights into the functional sites of human placental alkaline phosphatase, the structures of the enzyme with the putative regulators l -Phe, pNPP and 5,-AMP [Llinas et al. (2005), J. Mol. Biol.350, 441,451] were re-refined. Significant variations in ligand positioning and identity were found compared with the previous report. The multiple corrections to the model improved the phases and the electron-density maps, allowing the modeling of omitted side chains and multiple disordered residues. These improvements led to a change in the position of l -Phe at the peripheral binding site, which appeared to be reversed. The structure with pNPP contained only p -nitrophenol in three distinct sites, while the structure with 5,-AMP contained the p -nitrophenyl group in two of the sites instead of 5,-AMP. Comparison of the re-refined models shows a consistent pattern of interactions at the peripheral site. [source] | |||||||||||||