Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Aza-macrocyclic complexes have gained importance because of their pharmacological properties. Hexa-aza-macrocycles containing glutarimide efficiently coordinate as hexa-dentate ligand, to give complexes of Cu(II) possessing tetragonal structure and Mn(II), Co(II) and Ni(II) metal ions that are essentially octahedral. Spectroscopic, and chemical characterizations of these systems are presented in this article. For Ni(II) complexes results on electron transfer processes measured by cyclic voltammetry and colourimetry have been studied.
Spectrochim Acta A Mol Biomol Spectrosc 2005 Nov
PMID:EPR, UV-vis, magnetic, spectral studies and electrochemical behaviour of mononuclear transition metal complexes derived from novel hexa-aza-macrotricyclic ligand. 1625 58

Drought stress near heading reduces grain yield in rice cultivars by inhibiting processes such as anther dehiscence and panicle exsertion. Because cell-wall invertases play an important role in carbon allocation to developing organs, we examined the tissue-specific expression and drought sensitivity of the corresponding genes (OsCIN1-9) at heading in the widely grown cultivar IR64. OsCIN1-5,8 were expressed to varying degrees in flag leaf, panicle, anthers and peduncle at 1 day before heading (1 DBH). When water was withheld for 2 days starting 3 DBH, anthesis and peduncle elongation were halted. At the same time, transcript levels for OsCIN1-5,8 genes were all markedly down-regulated in anthers and/or peduncles but were not affected in flag leaves. Re-watering allowed anthesis and peduncle elongation to proceed and restored expression of OsCIN1-5,8. We conclude that cell-wall invertase genes, as a class, respond rapidly to water deficit in anthers and peduncles and through a reduction in sink strength help to coordinate a delay in anthesis and heading. By contrast, vacuolar invertase OsVIN2 was up-regulated by drought stress in flag leaves, panicles, anthers and peduncles. Although OsCIN1-3,5,8 were active in the peduncle, only OsCIN2 was expressed strongly and preferentially at the base, where cell division and cell elongation occur. OsCIN2 was expressed principally in the primary and secondary vascular systems, consistent with a role in diverting sucrose from the phloem to the dividing and expanding cells of the peduncle, whereas the less abundant OsCIN1,3,5,8 transcripts were found principally in parenchyma cells. The OsCIN2 transcript levels in the base were highest at 1 DBH, when rapid peduncle elongation began. Drought stress halted peduncle elongation and reduced OsCIN2 transcript level to 8% of the control level. On re-watering, peduncle elongation was restored and OsCIN2 transcript level recovered to 24% of the control. The abscisic acid (ABA) level of peduncles increased 7-fold on drought stress and returned to the control level on re-watering. Detached peduncles floated on water elongated little and lost all OsCIN2 transcripts, but on 50-100 microM GA3 they elongated rapidly and maintained high OsCIN2 transcript levels. ABA antagonized both peduncle elongation and maintenance of OsCIN2 transcript levels. We conclude that this antagonism is a potential intervention point for breeding strategies directed at enhancing panicle exsertion during or after drought stress at heading.
Plant Mol Biol 2005 Dec
PMID:Tissue-specific expression and drought responsiveness of cell-wall invertase genes of rice at flowering. 1630 68

From both steady state and fluorescence lifetime measurements it reveals that due to photoexcitation of benzotriazole (BZ) part of the bichromophore, 9(1-H-benzotriazole-lylmethyl)-9H-carbazole (BHC), singlet-singlet energy transfer takes place to populate the lowest excited singlet of carbazole (CZ). CZ, thus being excited indirectly via energy transfer process, undergoes strong charge transfer (CT) reaction with the surrounding polar medium acetonitrile (ACN). On the other hand, very weak CT band was apparent when CZ part, within BHC, was directly excited. In less polar tetrahydrofuran (THF) and polar benzonitrile (BN) environment, lack of formation of CT band strongly suggests in favor of the electron-accepting behavior of ACN. Moreover, by measuring the emission spectra of BHC in microcrystals and of 30 bilayers mixed LB film at high mole fraction of BHC molecules, the possibility of excimer formation or aggregation has been ruled out. Thus, BHC, when dissolved in ACN, acts as a triad system of BZ-CZ-ACN where BZ acts as an antenna molecule and CZ as a reaction center. The possible role of the bichromophoric system BHC as an artificial photosynthetic or solar energy conversion device has been hinted.
Spectrochim Acta A Mol Biomol Spectrosc 2007 Mar
PMID:Photophysical processes involved within the bichromophoric system 9-benzotriazole-1-ylmethyl-9H-carbazole and its role as an artificial photosynthetic device. 1685 57

Ethylene dibromide (EDB) is a widespread environmental pollutant and mutagen/carcinogen. Certain Theta-class glutathione transferases (GSTs), enzymes that catalyze the reaction of reduced glutathione (GSH) with electrophiles, activate EDB to a mutagen. Previous studies have shown that human GST T1-1, but not rat GST T2-2, activates EDB. We have constructed an E. coli lacZ reversion mutagenicity assay system in which expression of recombinant GST supports activation of EDB to a mutagen. Hexa-histidine N-terminal tagging of GST T1-1 results in greatly enhanced expression of the recombinant enzyme and gives a lacZ strain that shows a mutagenic response to EDB at extremely low levels (approximately 1 ng EDB per plate). The hexa-histidine-tagged enzyme was purified in one step by Ni(2+)-affinity chromatography. We applied the lacZ mutagenicity assay to the rapid screening of a library of variant GST Theta enzymes. Sequence variants with altered catalytic activities were identified, purified, and characterized.
Environ Mol Mutagen 2006 Dec
PMID:Screening and characterization of variant Theta-class glutathione transferases catalyzing the activation of ethylene dibromide to a mutagen. 1694 56

Infrared spectroscopy has been used to study the adsorption of para-nitrophenol on mono-, di- and tri-alkyl surfactant intercalated montmorillonite. Organoclays were obtained by the cationic exchange of mono-, di- and tri-alkyl chain surfactants for sodium ions [hexadecyltrimethylammonium bromide (HDTMAB), dimethyldioctadecylammonium bromide (DDOAB), methyltrioctadecylammonium bromide (MTOAB)] in an aqueous solution with Na-montmorillonite. Upon formation of the organoclay, the properties change from strongly hydrophilic to strongly hydrophobic. This change in surface properties is observed by a decrease in intensity of the OH stretching vibrations assigned to water in the cation hydration sphere of the montmorillonite. As the cation is replaced by the surfactant molecules, the para-nitrophenol replaces the surfactant molecules in the clay interlayer. Bands attributed to CH stretching and bending vibrations change for the surfactant intercalated montmorillonite. Strong changes occur in the HCH deformation modes of the methyl groups of the surfactant. These changes are attributed to the methyl groups locking into the siloxane surface of the montmorillonite. Such a concept is supported by changes in the SiO stretching bands of the montmorillonite siloxane surface. This study demonstrates that para-nitrophenol will penetrate into the untreated clay interlayer and replace the intercalated surfactant in surfactant modified clay, resulting in the change of the arrangement of the intercalated surfactant.
Spectrochim Acta A Mol Biomol Spectrosc 2008 Jan
PMID:An infrared study of adsorption of para-nitrophenol on mono-, di- and tri-alkyl surfactant intercalated organoclays. 1748 43

Human immunodeficiency virus tyoe 1 (HIV-1) Vif counteracts host restriction cytidine deaminase (APOBEC3G) A3G by co-opting the cellular ubiquitin-proteasome machinery. Vif utilizes a viral-specific BC-box to recruit ElonginB-ElonginC and a novel zinc-binding HCCH motif to recruit Cullin5 (Cul5) to form an E3 ubiquitin ligase targeting A3G for polyubiquitination and subsequently proteasomal degradation. To determine the structural requirements in HIV-1 Vif HCCH motif for Cul5 binding and Vif function, we investigated the arrangement of the His and Cys residues, the role of the spacing between them, and the requirement for the conserved residues. Our data demonstrate that exchanging Cys for His and vice versa in the highly conserved Zn-coordinating HCCH motif disrupted Vif function and interaction with Cul5. Moreover, the maintenance of both conserved residues and spacing within the HCCH motif is critical for Vif function. We have identified a "viral Cul5 box" with consensus Hx2YFxCFx4Phix2APhix7-8Cx5H that is required for Cul5 selection and subsequent A3G degradation. This novel motif may represent a potential new target for anti-viral drug development.
J Mol Biol 2007 Oct 26
PMID:Characterization of a novel Cullin5 binding domain in HIV-1 Vif. 1786 71

Plasma dopamine beta-hydroxylase activity (plDbetaH) is tightly regulated by the DBH gene and several genetic polymorphisms have been found to independently exert their influence. In the present investigation, association of four DBH polymorphisms, DBH-STR, rs1611115, rs1108580, and rs2519152 with plDbetaH was examined in blood samples from 100 unrelated individuals belonging to the state of West Bengal, Eastern India. Genotypes obtained after PCR amplification and restriction digestion were used for statistical analyses. plDbetaH was measured using a photometric assay and its correlation with the genetic polymorphisms was analyzed using analysis of variance and linear regression. Moderate linkage disequilibrium (LD) was observed between DBH-STR and rs1611115, while rs1108580 and rs2519152 were in strong LD. 'T' allele of rs1611115 showed strong negative correlation with plDbetaH, whereas DBH-STR, rs1108580 and rs2519152 had no major effect. Four haplotypes showed significant influence on plDbetaH. This is the first report on the effect of genetic polymorphisms on plDbetaH from the Indian sub-continent. rs1611115 was the only polymorphism that showed substantial control over plDbetaH. Other polymorphisms which did not show individual effects could possibly be part of larger haplotype blocks that carry the functional polymorphisms controlling plDbetaH.
Cell Mol Neurobiol 2008 May
PMID:Correlation of plasma dopamine beta-hydroxylase activity with polymorphisms in DBH gene: a study on Eastern Indian population. 1817 55

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset behavioral disorder with a definite genetic component. The search for genes predisposing to ADHD has focused on genes involved in the regulation of monoamine systems. In this study, we emphasized genes that underlie various aspects of dopamine, norepinephrine and serotonin neurotransmissions and performed a comprehensive association analysis by screening with 245 single-nucleotide polymorphisms (SNPs) of 23 candidate genes in a sample of Chinese Han descent. A total of 182 DSM-IV ADHD children and 184 healthy controls were genotyped and analyzed with an average density of one SNP every 6.1 kb. Both single-SNP and multi-marker haplotype analyses were implemented to exploit association signal for ADHD and its diagnostic subtypes. Empirical P-values were derived on the basis of 5000 permutations to evaluate gene-wide statistical significance. MAOA yielded highly suggestive evidence of association (empirical P<0.01, OR=1.94) with ADHD. For inattentive ADHD, MAOA, DDC and SYP showed suggestive evidence of association (empirical P<0.05). ADRA2C achieved suggestive significance (empirical P<0.05) for ADHD combined type. Additionally, for six genes (SNAP25, NET1, DBH, CHRNA4, DRD3 and SYT1) we detected one or more SNPs with nominal P-values</=0.05. This study has identified several genes as promising susceptibility loci for ADHD. Replication efforts and further investigations remain necessary to provide definite proof of association.
Mol Psychiatry 2009 May
PMID:A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population. 1818 Jul 57

Gamma-hexachlorocyclohexane (gamma-HCH), fipronil and picrotoxinin are noncompetitive antagonists (NCAs) of L-glutamate-gated chloride channels (GluCls), yet their potencies are weaker than those on gamma-aminobutyric acid receptors (GABARs). The A302S mutation of Drosophila RDL (resistant to dieldrin) GABAR confers NCA resistance, and housefly GluCls (MdGluCls) possess S278 as the residue corresponding to the A302. Thus, the effects of S278A mutation on the NCA actions on MdGluCls were investigated. The S278A mutation resulted in enhanced blocking by NCAs of the MdGluCl response to 30 microM L-glutamate. However, such actions of gamma-HCH and picrotoxinin, but not of fipronil, on the S278A mutant were reduced with 200 microM L-glutamate. Further increases in the L-glutamate concentration led to potentiation by NCAs of the mutant response to L-glutamate.
Insect Mol Biol 2008 Aug
PMID:Role of a serine residue (S278) in the pore-facing region of the housefly L-glutamate-gated chloride channel in determining sensitivity to noncompetitive antagonists. 1865 16

Signaling pathways involving cAMP and CREB have been implicated in several aspects of sympathetic neuron differentiation. Here, we used in vivo loss-of-function approaches in both mouse and chick embryos to characterize the physiological role of cAMP/CREB. Whereas sympathetic neuron development proceeds normally in CREB-deficient mouse embryos, a decrease in noradrenergic differentiation (TH, DBH) was observed in chick sympathetic ganglia in response to ACREB, a dominant-negative CREB variant which interferes with the function of all CREB family members. In contrast, expression of the generic neuronal marker SCG10 was not affected by ACREB. As the decrease in noradrenergic gene expression is compensated at later stages of development and TH expression in differentiated neurons is not CREB-dependent, a transient role for CREB is proposed, accelerating noradrenergic but not generic neuronal differentiation of sympathetic neurons.
Mol Cell Neurosci 2009 Oct
PMID:In vivo role for CREB signaling in the noradrenergic differentiation of sympathetic neurons. 1954 28


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