Mechanism of interaction of O-amino-D-serine with sheep liver serine hydroxymethyltransferase

The mechanism of interaction of 0-amino-D-serine (OADS) with sheep liver serine hydroxymethyltransferase (EC 2.1.2.1) (SHMT) was established by measuring changes in the enzyme activity,absorption spectra, circular dichroism (CD) spectra, and stopped-flow spectrophotometry. OADS was a reversible noncompetitive inhibitor (Ki = 1.8 pM) when serine was the varied substrate. The first step in the interaction of OADS with the enzyme was the disruption of enzyme-Schiff base, characterized by the rapid disappearance of absorbance at 425 nm (6.5 X lo3 M-' s-') and CD intensity at 430 nm. Concomitantly,there was a rapid increase in absorbance and CD intensity at 390 nm. The spectral properties of this intermediate enabled its identification as pyridoxal 5'-phosphate (PLP). These changes were followed by a slow unimolecular step (2 X s-') leading to the formation of PLP-OADS oxime, which was confirmed by its absorbance and fluorescence spectra and retention time on high-performance liquid chromatography. The PLP-OADS oxime was displaced from the enzyme by the addition of PLP as evidenced by the restoration of complete enzyme activity as well as by the spectral properties. The unique feature of the mechanism proposed for the interaction of OADS with sheep liver SHMT was the formation of PLP as an intermediate.

Mechanism of interaction of the antileukemic drug cytosine arabinoside with aromatic peptides : role of sugar conformation and peptide backbone

Interaction of the antileukemic drugs, cytosine-arabinoside (Ara-C) and adenosine-arabinoside (Ara-A) and a structural analogue, cytidine, with aromatic dipeptides has been studied by fluorescence and NMR spectroscopy. Ara-C and cytidine bind tryptophanyl and histidyl dipeptides but not tyrosyl dipeptides, while Ara-A does not bind to any of them. Both studies indicate association involving stacking of aromatic moieties. NMR spectra also indicate a protonation of the histidine moiety by Ara-C. In case of cytidine, the chemical shifts observed on binding to His-Phe imply that the backbone protons of the dipeptide participate in the binding. The conformation of the sugar and the base seem to play a very important role in the binding phenomenon as three similar molecules, Ara-C, Ara-A and cytidine bind in totally different ways.

Kinetics and mechanism of thermal decomposition of tetramethylammonium nitrate

The mechanism of thermal decomposition of tetramethylammonium nitrate has been investigated by thermogravimetry and mass spectrometry. The activation energy for the decomposition has been determined by isothermal decomposition technique using thermogravimetry and by monitoring mass spectrometrically the formation of trimethylamine. The activation energies determined in both the cases compare well, suggesting that the decomposition proceeds via dissociation of tetramethylammonium nitrate into trimethylamine and methylnitrate.

An excitonic mechanism for high-temperature. Superconductivity in YBa2Cu3O7

We propose an excitonic mechanism for high temperature superconductivity in YBa2Cu3O7. We feel that in this material, nature has provided a very elegant system, closely simulated by the model proposed by Allender, Bray and Bardeen1 using Ginzburg's ideas.2 In this system the excitonic layer and the conduction electron layers are indeed atomic planes making contacts on atomic level, an ideal version of the situation envisaged by Allender et al. Further, since these layers are physically separated, the question of screening of charges is avoided.

Use of 2-pyrimidineamidoxime to generate polynuclear homo-/heterometallic assemblies: synthesis, crystal structures and magnetic study with theoretical investigations on the exchange mechanism

Three new transition metal complexes using 2-pyrimidineamidoxime (pmadH(2)) as multidentate chelating and/or bridging ligand have been synthesized and characterized. The ligand pmadH(2) has two potential bridging functional groups mu-O and mu-(N-O)] and consequently shows several coordination modes. While a polymeric 1D Cu-II complex Cu(pmadH(2))(2)(NO3)](NO3) (1) was obtained upon treatment of Cu(NO3)(2)center dot 3H(2)O with pmadH(2) at room temperature in the absence of base, a high temperature reaction in the presence of base yielded a tetranuclear Cu-II-complex Cu-4(pmad)(2)(pmadH)(2)(NO3)](NO3)(H2O) (2). One of the Cu-II centers is in a square pyramidal environment while the other three are in a square planar geometry. Reaction of the same ligand with an equimolar mixture of both Cu(NO3)(2)center dot 3H(2)O and NiCl2 center dot 6H(2)O yielded a tetranuclear heterometallic (Cu2Ni2II)-Ni-II complex Cu2Ni2(pmad)(2)(pmadH)(2)Cl-2]center dot H2O (3) containing both square planar (Ni-II) and square pyramidal (Cu-II) metal centers. Complexes 1-3 represent the first examples of polynuclear metal complexes of 2-pyrimidineamidoxime. The analysis of variable temperature magnetic susceptibility data of 2 reveals that both ferromagnetic and antiferromagnetic interactions exist in this complex (J(1) = +10.7 cm(-1) and J(2) = -2.7 cm(-1) with g = 2.1) leading to a resultant ferromagnetic behavior. Complex 3 shows expected antiferromagnetic interaction between two Cu-II centers through -N-O- bridging pathway with J(1) = -3.4 cm(-1) and g = 2.08. DFT calculations have been used to corroborate the magnetic results.

Facile hydrothermal synthesis and observation of bubbled growth mechanism in nano-ribbons aggregated microspherical Covellite blue-phosphor

Well uniform microspheres of phase pure Covellite were synthesized through a simple hydrothermal approach using poly vinyl pyrrolidone (PVP) as surfactant. The micro-spheres were constituted of numerous self-organized knitted nano-ribbons of similar to 30 nm thickness. The effect of conc. PVP in the hydrothermal precursor solution on the product morphology was investigated. Based on the out-coming product micro-architecture a growth mechanism was proposed which emphasized bubbled nucleation inside the hydrothermal reactor. In a comparative study on linear optical properties, enhancement of luminescent intensity was observed for nano-ribbon clung microspheres rather than that of agglomerates of distorted particles, which may be attributed to better crystallinity as well as reduced surface defects and ionic vacancies for ribbon-like nano-structures.

A Triggering Mechanism for Enhanced Star-Formation in Colliding Galaxies

We propose a physical mechanism to explain the origin of the intense burst of massive-star formation seen in colliding/merging, gas-rich, field spiral galaxies. We explicitly take account of the different parameters for the two main mass components, H-2 and H I, of the interstellar medium within a galaxy and follow their consequent different evolution during a collision between two galaxies. We also note that, in a typical spiral galaxy-like our galaxy, the Giant Molecular Clouds (GMCs) are in a near-virial equilibrium and form the current sites of massive-star formation, but have a low star formation rate. We show that this star formation rate is increased following a collision between galaxies. During a typical collision between two field spiral galaxies, the H I clouds from the two galaxies undergo collisions at a relative velocity of approximately 300 km s-1. However, the GMCs, with their smaller volume filling factor, do not collide. The collisions among the H I clouds from the two galaxies lead to the formation of a hot, ionized, high-pressure remnant gas. The over-pressure due to this hot gas causes a radiative shock compression of the outer layers of a preexisting GMC in the overlapping wedge region. This makes these layers gravitationally unstable, thus triggering a burst of massive-star formation in the initially barely stable GMCs.The resulting value of the typical IR luminosity from the young, massive stars from a pair of colliding galaxies is estimated to be approximately 2 x 10(11) L., in agreement with the observed values. In our model, the massive-star formation occurs in situ in the overlapping regions of a pair of colliding galaxies. We can thus explain the origin of enhanced star formation over an extended, central area approximately several kiloparsecs in size, as seen in typical colliding galaxies, and also the origin of starbursts in extranuclear regions of disk overlap as seen in Arp 299 (NGC 3690/IC 694) and in Arp 244 (NGC 4038/39). Whether the IR emission from the central region or that from the surrounding extranuclear galactic disk dominates depends on the geometry and the epoch of the collision and on the initial radial gas distribution in the two galaxies. In general, the central starburst would be stronger than that in the disks, due to the higher preexisting gas densities in the central region. The burst of star formation is expected to last over a galactic gas disk crossing time approximately 4 x 10(7) yr. We can also explain the simultaneous existence of nearly normal CO galaxy luminosities and shocked H-2 gas, as seen in colliding field galaxies.This is a minimal model, in that the only necessary condition for it to work is that there should be a sufficient overlap between the spatial gas distributions of the colliding galaxy pair.

Computer modelling studies on the mechanism of action of ribonuclease T1

The mechanism of action of ribonuclease (RNase) T1 is still a matter of considerable debate as the results of x-ray, 2-D nmr and site-directed mutagenesis studies disagree regarding the role of the catalytically important residues. Hence computer modelling studies were carried out by energy minimisation of the complexes of RNase T1 and some of its mutants (His40Ala, His40Lys, and Glu58Ala) with the substrate guanyl cytosine (GpC), and of native RNase T1 with the reaction intermediate guanosine 2',3'-cyclic phosphate (G greater than p). The puckering of the guanosine ribose moiety in the minimum energy conformer of the RNase T1-GpC (substrate) complex was found to be O4'-endo and not C3'-endo as in the RNase T1-3'-guanylic acid (inhibitor/product) complex. A possible scheme for the mechanism of action of RNase T1 has been proposed on the basis of the arrangement of the catalytically important amino acid residues His40, Glu58, Arg77, and His92 around the guanosine ribose and the phosphate moiety in the RNase T1-GpC and RNase T1-G greater than p complexes. In this scheme, Glu58 serves as the general base group and His92 as the general acid group in the transphosphorylation step. His40 may be essential for stabilising the negatively charged phosphate moiety in the enzyme-transition state complex.

One pot synthesis of polycyclic oxygen aromatics. Part III mechanism of formation

Reaction of 6-Image -butyl-1-bromomethyl-2-(2-tetrahydropyranyloxy)-naphthalene2c with tetrachlorocatechol (TCC) in acetone in presence of K2CO3 gave diastereomers 6c and 7c. A mechanism (Scheme-1) invoking the base induced cleavage of the pyranyl ether 2 to 1,2-naphthoquinone-1-methide 8 as the first step has been postulated. The cleavage of the pyranyl ether linkage in 2 to give dimers 4 and 5 of 1,2-naphthoquinone-1-methide has been demonstrated with different bases. 1,2-Naphthoquinone-1-methide 8, thus generated, undergoes Michael addition with TCC followed by elimination of chloride ions to give a diketone, which further undergoes aldolisation with acetone to give diastereomers 6 and 7. Michael reaction of 8, generated Image from pyranyl ethers 2a-c, with tetrabromocatechol (TBC) under similar-reaction conditions gave the expected monobromo compounds 6h, 6i, 6k, 7n, 7n and 7q. The last step in the proposed mechanism, Image ., aldolisation has also been demonstrated using different ketonic solvents. Thus, reaction of 2a-c with TCC/TBC in diethyl ketone/methyl ethyl ketone under similar reaction conditions gave the expected compounds 6 and 7.

The Mechanism Of The Hydrogen Abstraction Process By Photo-Excited Ketones

Qualitative potential energy surfaces for hydrogen abstraction from alkanes containing primary, secondary and tertiary C-H bonds by a photo-excited ketone have been reported, The results suggest that the activation barriers for these processes decrease in the order primary > secondary > tertiary in agreement with the observed trend in the rate constants. The analysis of the electronic structure of the transition-state reveal that electron-transfer from hydrocarbon to ketone and formation of a new bond are almost synchronous in the hydrogen transfer process. The tunneling of hydrogen is not important in the normal temperature region even though the barriers are small.

Tonically Active Kainate Receptors (tKARs) : A Novel Mechanism Regulating Neuronal Function in the Brain

Fast excitatory transmission between neurons in the central nervous system is mainly mediated by L-glutamate acting on ligand gated (ionotropic) receptors. These are further categorized according to their pharmacological properties to AMPA (2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid), NMDA (N-Methyl-D-aspartic acid) and kainate (KAR) subclasses. In the rat and the mouse hippocampus, development of glutamatergic transmission is most dynamic during the first postnatal weeks. This coincides with the declining developmental expression of the GluK1 subunit-containing KARs. However, the function of KARs during early development of the brain is poorly understood. The present study reveals novel types of tonically active KARs (hereafter referred to as tKARs) which play a central role in functional development of the hippocampal CA3-CA1 network. The study shows for the first time how concomitant pre- and postsynaptic KAR function contributes to development of CA3-CA1 circuitry by regulating transmitter release and interneuron excitability. Moreover, the tKAR-dependent regulation of transmitter release provides a novel mechanism for silencing and unsilencing early synapses and thus shaping the early synaptic connectivity. The role of GluK1-containing KARs was studied in area CA3 of the neonatal hippocampus. The data demonstrate that presynaptic KARs in excitatory synapses to both pyramidal cells and interneurons are tonically activated by ambient glutamate and that they regulate glutamate release differentially, depending on target cell type. At synapses to pyramidal cells these tKARs inhibit glutamate release in a G-protein dependent manner but in contrast, at synapses to interneurons, tKARs facilitate glutamate release. On the network level these mechanisms act together upregulating activity of GABAergic microcircuits and promoting endogenous hippocampal network oscillations. By virtue of this, tKARs are likely to have an instrumental role in the functional development of the hippocampal circuitry. The next step was to investigate the role of GluK1 -containing receptors in the regulation of interneuron excitability. The spontaneous firing of interneurons in the CA3 stratum lucidum is markedly decreased during development. The shift involves tKARs that inhibit medium-duration afterhyperpolarization (mAHP) in these neurons during the first postnatal week. This promotes burst spiking of interneurons and thereby increases GABAergic activity in the network synergistically with the tKAR-mediated facilitation of their excitatory drive. During development the amplitude of evoked medium afterhyperpolarizing current (ImAHP) is dramatically increased due to decoupling tKAR activation and ImAHP modulation. These changes take place at the same time when the endogeneous network oscillations disappear. These tKAR-driven mechanisms in the CA3 area regulate both GABAergic and glutamatergic transmission and thus gate the feedforward excitatory drive to the area CA1. Here presynaptic tKARs to CA1 pyramidal cells suppress glutamate release and enable strong facilitation in response to high-frequency input. Therefore, CA1 synapses are finely tuned to high-frequency transmission; an activity pattern that is common in neonatal CA3-CA1 circuitry both in vivo and in vitro. The tKAR-regulated release probability acts as a novel presynaptic silencing mechanism that can be unsilenced in response to Hebbian activity. The present results shed new light on the mechanisms modulating the early network activity that paves the way for oscillations lying behind cognitive tasks such as learning and memory. Kainate receptor antagonists are already being developed for therapeutic use for instance against pain and migraine. Because of these modulatory actions, tKARs also represent an attractive candidate for therapeutic treatment of developmentally related complications such as learning disabilities.