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        Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives

        Shuqun Zhang,Bo Hou,Huaiyu Yang,Zhili Zuo 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.5

        Acetylcholinesterase (AChE) is an importantenzyme in the pathogenesis of Alzheimer’s disease (AD). Comparative quantitative structure-activity relationship(QSAR) analyses on some huprines inhibitors againstAChE were carried out using comparative molecular fieldanalysis (CoMFA), comparative molecular similarityindices analysis (CoMSIA), and hologram QSAR(HQSAR) methods. Three highly predictive QSAR modelswere constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have valuesof r2 = 0.988, q2 = 0.757, ONC = 6; r2 = 0.966, q2 =0.645, ONC = 5; and r2 = 0.957, q2 = 0.736, ONC = 6. The predictabilities were validated using an external testsets, and the predictive r2 values obtained by the threemodels were 0.984, 0.973, and 0.783, respectively. Theanalysis was performed by combining the CoMFA andCoMSIA field distributions with the active sites of theAChE to further understand the vital interactions betweenhuprines and the protease. On the basis of the QSAR study,14 new potent molecules have been designed and six ofthem are predicted to be more active than the best activecompound 24 described in the literature. The final QSARmodels could be helpful in design and development ofnovel active AChE inhibitors.

      • Mitogen-activated protein kinase cascade in the signaling for polyamine biosynthesis in tobacco.

        Jang, Eun-Kyoung,Min, Kwang-Hyun,Kim, Su-Hyun,Nam, Seung-Hee,Zhang, Shuqun,Kim, Young Cheol,Cho, Baik Ho,Yang, Kwang-Yeol Japanese Society of Plant Physiologists 2009 Plant & cell physiology Vol.50 No.3

        <P>Expression of NtNEK2(DD), a constitutively active mutant of NtMEK2, activates endogenous salicylic acid-induced protein kinase (SIPK) and wounding-induced protein kinase (WIPK), and leads to several stress/defense responses in tobacco. In this study, we used ACP (annealing control primer)-based differential display reverse transcription-PCR to isolate the downstream effectors mediated by the NtMEK2-SIPK/WIPK cascade. The arginine decarboxylase gene (ADC), which is involved in plant putrescine biosynthesis, was one of nine differentially expressed genes. When compared with NtMEK2(KR) plants, NtMEK2(DD) transgenic plants exhibited a significant increase in ADC and ODC (ornithine decarboxylase) transcript levels, as well as in putrescine and its catabolite, gamma-aminobutyric acid, following SIPK/WIPK activation. Taken together, these results suggest that the NtMEK2-SIPK/WIPK cascade is involved in regulating polyamine synthesis, especially putrescine synthesis, through transcriptional regulation of the biosynthetic genes in tobacco.</P>

      • Regulation of floral organ abscission of Arabidopsis thaliana

        Sung Ki Cho,David Chevalier,Clayton Larue,Tsung-Luo Jinn,Shuqun Zhang,John C. Walker 한국작물학회 2007 한국작물학회 학술발표대회 논문집 Vol.2007 No.11

        Organ abscission is a programmed cell separation process that results in the detachment of an entire organ from a plant. Our goal is to understand the signaling pathway that regulates this physiological process. The receptor-like protein kinase, HAESA (HAE), and its paralog, HAESA-like 2 (HSL2), are both expressed in the floral abscission zones in Arabidopsis thaliana. Loss-of-function analyses of either gene do not show any phenotypical change, but the hae hsl2 double mutant shows an abscission-defect phenotype. Examination of the abscission zone by light and scanning electron microscopy showed that the abscission zone in the hae hsl2 appears structurally normal. The force required to remove the petals in wild type and hae hsl2 flowers was measured using a petal breakstrength meter. The force required to remove petals from the hae hsl2flowers at all stages of development was similar to that of wild type flowers that have not yet begun to abscise their petals. Taken together, these data support the role of HAE and HSL2 in the activation of cell separation, rather than differentiation of the abscission zone. Ethylene is also known to promote abscission; therefore we tested the ethylene-induced triple response and the effect of exogenous treatment on floral organ in the hae hsl2, revealing that HAE and HSL2 act independently of ethylene. This implies that the HAE is critical for floral abscission in concert with the action of HSL2.

      • Mitogen-activated protein kinase 3 and 6 regulate <i>Botrytis cinerea</i>-induced ethylene production in Arabidopsis

        Han, Ling,Li, Guo-Jing,Yang, Kwang-Yeol,Mao, Guohong,Wang, Ruigang,Liu, Yidong,Zhang, Shuqun Blackwell Publishing Ltd 2010 The Plant journal Vol.64 No.1

        <P>Summary</P><P>Plants challenged by pathogens, especially necrotrophic fungi such as <I>Botrytis cinerea</I>, produce high levels of ethylene. At present, the signaling pathways underlying the induction of ethylene after pathogen infection are largely unknown. MPK6, an Arabidopsis stress-responsive mitogen-activated protein kinase (MAPK) was previously shown to regulate the stability of ACS2 and ACS6, two type I ACS isozymes (1-amino-cyclopropane-1-carboxylic acid synthase). Phosphorylation of ACS2 and ACS6 by MPK6 prevents rapid degradation of ACS2/ACS6 by the 26S proteasome pathway, resulting in an increase in cellular ACS activity and ethylene biosynthesis. Here, we show that MPK3, which shares high homology and common upstream MAPK kinases with MPK6, is also capable of phosphorylating ACS2 and ACS6. In the <I>mpk3</I> mutant background, ethylene production in gain-of-function <I>GVG-NtMEK2</I><SUP><I>DD</I></SUP> transgenic plants was compromised, suggesting that MPK6 and MPK3 function together to stabilize ACS2 and ACS6. Using a liquid-cultured seedling system, we found that <I>B. cinerea</I>-induced ethylene biosynthesis was greatly compromised in <I>mpk3/mpk6</I> double mutant seedlings. In contrast, ethylene production decreased only slightly in the <I>mpk6</I> single mutant and not at all in the <I>mpk3</I> single mutant, demonstrating overlapping roles for these two highly homologous MAPKs in pathogen-induced ethylene induction. Consistent with the role of MPK3/MPK6 in the process, mutation of <I>ACS2</I> and <I>ACS6</I>, two genes encoding downstream substrates of MPK3/MPK6, also reduced <I>B. cinerea</I>-induced ethylene production. The residual levels of ethylene induction in the <I>acs2/acs6</I> double mutant suggest the involvement of additional ACS isoforms, possibly regulated by MAPK-independent pathway(s).</P>

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