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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Bacillus subtilis, the termination of DNA replication via polar fork arrest is effected by a specific protein:DNA complex formed between the replication terminator protein (RTP) and DNA terminator sites. We report the crystal structure of a replication terminator protein homologue (RTP.C110S) of B. subtilis in complex with the high affinity component of one of its cognate DNA termination sites, known as the TerI B-site, refined at 2.5 A resolution. The 21 bp RTP:DNA complex displays marked structural asymmetry in both the homodimeric protein and the DNA. This is in contrast to the previously reported complex formed with a symmetrical TerI B-site homologue. The induced asymmetry is consistent with the complex's solution properties as determined using NMR spectroscopy. Concomitant with this asymmetry is variation in the protein:DNA binding pattern for each of the subunits of the RTP homodimer. It is proposed that the asymmetric "wing" positions, as well as other asymmetrical features of the RTP:DNA complex, are critical for the cooperative binding that underlies the mechanism of polar fork arrest at the complete terminator site.
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PMID:An asymmetric structure of the Bacillus subtilis replication terminator protein in complex with DNA. 1752 68

Porphyrins play a major role as active photosensitizers in noninvasive optical photodynamic therapy (PDT). In a modular approach, this paper presents a short review of the recent developments of porphyrin structures and materials with improved photosensitizing properties and then presents the synthesis and characterization of a series of new second generation asymmetrical meso-tetraphenylporphyrins varied by substituent in the meta positions of the phenyl rings with either -OH or -OCH3 groups, whereas in the para positions only with -OCH3 groups. The new series of differentially functionalized porphyrins were obtained by a combinatorial multicomponent synthesis (Adler-Longo method) by simultaneously using two different aldehydes: 3,4-dimethoxybenzaldehyde and 3-hydroxybenzaldehyde. The porphyrins were isolated, purified and characterized by HPLC, TLC, UV-vis, fluorescence, MS, 1H-NMR, and 13C-NMR analysis, accompanied by DEPT 135 experiments. Because of the fact that the medium in cancerous tissues is often more acidic than in normal tissues, the capacity of these porphyrins to exist simultaneously in aggregated and protonated forms was also investigated, in tetrahydrofuran (THF) and acid THF-water systems, underlying the changes in the photophysical behaviour. The relative fluorescence quantum yields (Phif) were calculated in comparison with meso-tetraphenylporphyrin (TPP), and the values between 0.14-0.26 were found to be promising for further trials. The series of asymmetrically substituted tetraphenylporphyrins, as the new class of supramolecular materials, are suitable for further functionalization in order to improve their photophysical properties, and they could represent interesting potential PDT photosensitizers.
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PMID:Combinatorial synthesis and characterization of new asymmetric porphyrins as potential photosensitizers in photodynamic therapy. 1789 42

The SL1 stem-loop is the dimerization initiation site for linking the two copies of the RNA forming the HIV-1 genome. The 26 nucleotides stem contains a defect consisting on a highly conserved G-rich 1-3 asymmetrical internal loop, which is a major site for nucleocapsid protein binding. Several NMR attempts were undertaken to determine the internal loop structure in the SL1 monomer. However, the RNA constructs used in the different studies were largely mutated, in particular with replacement of the nine nucleotides apical loop by a tetraloop, and divergent results were obtained ranging from a rigid structure to a particularly large flexibility. To investigate the reasons for such discrepancies, we used molecular dynamics simulation of the SL1 monomer to probe the effect of mutations on the conformational stability of the internal loop and of the whole stem. It is found that in the wild-type sequence, the internal loop displays conformational variability originating mainly from the nine nucleotides apical loop flexibility that causes large conformational fluctuations (without changing the average structure) in the 7 bp duplex linking the apical and internal loops. The large amplitude atomic motions in the duplex are transmitted to the internal loop in which they induce conformational changes characterized by a labile hydrogen bond network such as G5 successively H-bonded to A29 and G30. On the contrary, with a four nucleotides apical loop, conformational fluctuations in the duplex are reduced by a factor of 2 and are not sufficiently energizing for promoting changes in the internal loop structure at the time scale of the simulations.
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PMID:Insight into the intrinsic flexibility of the SL1 stem-loop from genomic RNA of HIV-1 as probed by molecular dynamics simulation. 1800 23

The new cerium(III), lanthanum(III) and neodymium(III) complexes were synthesized in view of their application as cytotoxic agents. The complexes were characterized by different physicochemical methods: elemental analysis, mass spectrometry, (1)H NMR, (13)C NMR and IR spectroscopy. The spectra of the complexes were interpreted on the basis of comparison with the spectrum of the free ligand. The vibrational analysis showed that in the complexes the ligand coordinates to the metal ion through both deprotonated hydroxyl groups, however participation of the carbonyl groups in the coordination to the metal ion was also suggested. Geometry optimization of 3,3'-(ortho-pyridinomethylene)di-[4-hydroxycoumarin] H(2)(o-pyhc), (H(2)L) and its dianionic forms, o-pyhc(2-), (L(2-)) were carried out at AM1 and PM3 levels as well as using density functional theory with Becke's three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with 6-31G(d) basis set. The optimized geometries of the neutral ligand isomers were stabilized by two asymmetrical intramolecular O-H...O hydrogen bonds (HBs). The conformational search showed four low-energy dianionic species (o-pyhc(2-)) on the potential energy surface. Molecular electrostatic potential calculations showed that the most preferred sites for electrophilic attack in H(2)(o-pyhc) and o-pyhc(2-) are the carbonyl oxygen atoms. The evaluation of the cytotoxic activity of the novel lantanide complexes on HL-60 myeloid cells revealed, that they are potent cytotoxic agents. The cerium complex was found to exhibit superior activity in comparison to the lanthanum, and neodymium species, the latter being the least active. Taken together our data give us a reason to conclude that the newly synthesized lanthanide complexes should be a subset to further more detailed pharmacological and toxicological evaluation.
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PMID:Theoretical, spectral characterization and antineoplastic activity of new lanthanide complexes. 1856 22

The concept that the basic unit of all life, the cell, is a membrane-enclosed soup of (free) water, (free) K+ (and native) proteins is called the membrane theory. A careful examination of past records shows that this theory has no author in the true sense of the word. Rather, it grew mostly out of some mistaken ideas made by Theodor Schwann in his Cell Theory. (This is not to deny that there is a membrane theory with an authentic author but this authored membrane theory came later and is much more narrowly focussed and accordingly can at best be regarded as an offshoot of the broader and older membrane theory without an author.) However, there is no ambiguity on the demise of the membrane theory, which occurred more than 60 years ago, when a flood of converging evidence showed that the asymmetrical distribution of K+ and Na+ observed in virtually all living cells is not the result of the presence of a membrane barrier that permits some solutes like water and K+ to move in and out of the cell, while barring--absolutely and permanently--the passage of other solutes like Na+. To keep the membrane theory afloat, submicroscopic pumps were installed across the cell membrane to maintain, for example, the level of Na+ in the cell low and the level of K+ high by the ceaseless pumping activities at the expense of metabolic energy. Forty-five year ago this version of the membrane theory was also experimentally disproved. In spite of all these overwhelming evidence against the membrane-pump theory, it still is being taught as verified truth in all high-school and biology textbooks known to us today. Meanwhile, almost unnoticed, a new unifying theory of the living cell, called the association-induction hypothesis came into being some 40 years ago. Also little noticed was the fact that it has received extensive confirmation worldwide and has shown an ability to provide self-consistent interpretations of most if not all known experimental observations that are contradicting the membrane-pump theory as well as other observations that seem to support the membrane pump theory.
Physiol Chem Phys Med NMR 2007
PMID:History of the membrane (pump) theory of the living cell from its beginning in mid-19th century to its disproof 45 years ago--though still taught worldwide today as established truth. 1861 39

Synthesis and spectroscopic studies on four-coordinate complexes of cadmium(II) and mercury(II) halides with a new asymmetrical bidentate Schiff base ligand of N,N'-bis[alpha-methylcinamaldehydene]propane-1,2-diamine(L) are described. The ligand and its complexes were characterized by elemental analysis, molar conductance, UV-visible spectra, FT-IR spectra, MS, (1)H NMR and (13)C NMR spectra. The complexes are non-electrolytes in DMF. The electronic spectra of the complexes were recorded in DMF solution. (1)H and (13) C NMR spectra been studied in CDCl(3). The molar conductance as well as spectral properties indicated the complexes do not dissociate in DMF and retain their coordination. FT-IR and NMR spectra of the complexes exhibit downfield as well as upfield shifts of the free ligand resonances that show change in geometry during the coordination. The suggested structure of the complexes is pseudo-tetrahedral. Molecular structures of the complexes have been optimized by MM+ calculations that supported pseudo-tetrahedral geometry around the metal (II) ions.
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PMID:Synthesis and spectroscopic studies of some cadmium(II) and mercury(II) complexes of an asymmetrical bidentate Schiff base ligand. 1930 52

A new class of dendron-like polypeptide/linear poly(epsilon-caprolactone) block copolymers with asymmetrical topology (i.e., dendron-like poly(gamma-benzyl-l-glutamate)/linear PCL copolymers having 2(m) PBLG branches, m = 0, 1, 2, and 3; denoted as PCL-Dm-PBLG) was for the first time synthesized via the combination of controlled ring-opening polymerization (ROP) of epsilon-caprolactone, click chemistry, and the ROP of gamma-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA). The linear hydroxyl-terminated PCL (PCL-OH) was synthesized by controlled ROP of epsilon-caprolactone and then transformed into clickable azide-terminated PCL (PCL-N(3)). The PCL-N(3) precursor was further click conjugated with propargyl focal point PAMAM-typed dendrons (i.e., Dm having 2(m) primary amine groups) to generate PCL-dendrons (PCL-Dm) using CuBr/PMDETA as catalyst in dimethylformamide solution at 35 degrees C. Finally, PCL-Dm was used as macroinitiator for the ROP of BLG-NCA monomer to produce the targeted PCL-Dm-PBLG block copolymers. Their molecular structures and physical properties were characterized in detail by FT-IR, NMR, matrix assisted laser desorption ionization time-of-flight mass spectrometry, gel permeation chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. To the best of our knowledge, this is the first report that describes the synthesis of dendron-like polypeptide/linear PCL block copolymers with asymmetrical topology via the combination of ROP and click chemistry. Consequently, this provides a versatile strategy for the synthesis of biodegradable and biomimetic dendron-like polypeptide-based biohybrids.
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PMID:Versatile strategy for the synthesis of dendronlike polypeptide/linear poly(epsilon-caprolactone) block copolymers via click chemistry. 1932 56

Cadmium(II) cysteinate compounds have recently been recognized to provide an environmentally friendly route for the production of CdS nanoparticles, used in semiconductors. In this article, we have studied the coordination for two cadmium(II) cysteinates, Cd(HCys)(2) x H(2)O (1) and {Cd(HCys)(2) x H(2)O}(2) x H(3)O(+)ClO(4)(-) (2), by means of vibrational (Raman and IR absorption), solid-state NMR ((113)Cd and (13)C), and Cd K- and L(3)-edge X-ray absorption spectroscopy. Indistinguishable Cd K-edge extended X-ray absorption fine structure (EXAFS) and Cd L(3)-edge X-ray absorption near edge structure (XANES) spectra were obtained for the two compounds, showing similar local structure around the cadmium(II) ions. The vibrational spectra show that the cysteine amine group is protonated (NH(3)(+)) and not involved in bonding. The (113)Cd solid-state cross-polarization magic angle spinning NMR spectra showed a broad signal in the approximately 500-700 ppm range, with the peak maximum at about 650 ppm, indicating three to four coordinated thiolate groups. Careful analyses of low-frequency Raman and far-IR spectra revealed bridging and terminal Cd-S vibrational bands. The average Cd-S distance of 2.52 +/- 0.02 A that constantly emerged from least-squares curve-fitting of the EXAFS spectra is consistent with CdS(4) and CdS(3)O coordination. Both structural models yielded reasonable values for the refined parameters, with a slightly better fit for the CdS(3)O configuration, for which the Cd-O distance of 2.27 +/- 0.04 A was obtained. The Cd L(3)-edge XANES spectra of 1 and 2 resembled that of the CdS(3)O model compound and showed that the coordination around Cd(II) ions in 1 and 2 cannot be exclusively CdS(4). The small separation of 176 cm(-1) between the infrared symmetric and antisymmetric COO(-) stretching modes indicates monodentate or strongly asymmetrical bidentate coordination of a cysteine carboxylate group in the CdS(3)O units. The combined results are consistent with a "cyclic/cage" type of structure for both the amorphous solids 1 and 2, composed of CdS(4) and CdS(3)O units with single thiolate (Cd-S-Cd) bridges, although a minor amount of cadmium(II) sites with CdS(3)O(2-3) and CdS(4)O coordination geometries cannot be ruled out.
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PMID:Cadmium(II) cysteine complexes in the solid state: a multispectroscopic study. 1935 Nov 34

The physicochemical characteristics of the ultra-high viscosity and highly biocompatible alginates extracted from Lessonia nigrescens (UHV(N)) and Lessonia trabeculata (UHV(T)) were analyzed. Fluorescence and (1)H NMR spectroscopies, viscometry, and multi-angle light scattering (MALS) were used for elucidation of the chemical structure, molar mass, and coil size. The sequential structures from NMR spectroscopy showed high guluronate content for UHV(T), but low for UHV(N). Intrinsic viscosity [eta] measurements exhibited unusual high values (up to 2750 mL/g), whereas [eta] of a commercial alginate was only about 970 mL/g. MALS batch measurements of the UHV-alginates yielded ultra-high values of the weight average molar mass (M(w) up to 1.1x10(6) g/mol) and of the z-average gyration radius (R(G)(z) up to 191 nm). The M(w) and R(G)(z) distributions of UHV-alginates and of ultrasonically degraded fractions were determined using size exclusion chromatography combined with MALS and asymmetrical flow-field-flow fractionation. The M(w) dependency of [eta] and R(G)(z) could be described by [eta]=0.059xM(w)(0.78) and R(G)(z)=0.103xM(w)(x). (UHV(N): x=0.52; UHV(T): x=0.53) indicating that the monomer composition has no effect on coil expansion. Therefore, the equations can be used to calculate M(w) and R(G)(z) values of UHV(T)- and UHV(N)-alginate mixtures as used in immunoisolation. Furthermore, the simple and inexpensive capillary viscometry can be used for real-time validation of the extraction and purification process of the UHV-alginates.
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PMID:Physicochemical features of ultra-high viscosity alginates. 1939 90

Novel inhibitors of lupin diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) hydrolase have been identified by in silico screening of a large virtual chemical library. Compounds were ranked on the basis of a consensus from six scoring functions. From the top 100 ranked compounds six were selected and initially screened for inhibitory activity using a single concentration isothermal titration calorimetry assay. Two of these compounds that showed excellent solubility properties were further analyzed, but only one [NSC51531; 2-((8-hydroxy-4-(4-methyl-2-sulfoanilino)-9,10-dioxo-9,10-dihydro-1-anthracenyl)amino)-5-methylbenzenesulfonic acid] exhibited competitive inhibition with a K(i) of 1 microM. A structural analogue of this compound also exhibited competitive inhibition with a comparable K(i) of 2.9 microM. (1)H, (15)N NMR spectroscopy was used to map the binding site of NSC51531 on lupin Ap(4)A hydrolase and demonstrated that the compound bound specifically in the substrate-binding site, consistent with the competitive inhibition results. Binding of NSC51531 to the human form of Ap(4)A hydrolase is nonspecific, suggesting that this compound may represent a useful lead in the design of specific inhibitors of the plant-like form of Ap(4)A hydrolases.
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PMID:Discovery of inhibitors of lupin diadenosine 5',5'''-P(1),P(4)-tetraphosphate hydrolase by virtual screening. 1960 90


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