Pharmacophore-based virtual screening and experimental validation of novel inhibitors against cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase.


:Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (cy-FBP/SBPase) is a potential enzymatic target for screening of novel inhibitors that can combat harmful algal blooms. In the present study, we targeted the substrate binding pocket of cy-FBP/SBPase. A series of novel hit compounds from the SPECs database were selected by using a pharmacophore-based virtual screening strategy. Most of the compounds tested exhibited moderate inhibitory activities (IC50 = 20.7-176.9 μM) against cy-FBP/SBPase. Compound 2 and its analogues 10 and 11 exhibited strong inhibitory activities, with IC50 values of 20.7, 13.4, and 19.0 μM against cy-FBP/SBPase in vitro and EC50 values of 12.3, 10.9, and 2.9 ppm against cyanobacteria Synechocystis PCC6803 in vivo, respectively. The compound 10 was selected in order to perform a refined docking study to investigate the rational binding mode of inhibitors with cy-FBP/SBPase. Furthermore, possible interactions of the residues with inhibitors were examined by site-directed mutagenesis, enzymatic assays, and fluorescence spectral analyses. The results provide insight into the binding mode between the inhibitors and the substrate binding pocket. The observed theoretical and experimental results are in concert, indicating that the modeling strategies and screening methods employed are appropriate to search for novel lead compounds having both structural diversity and high inhibitory activity against cy-FBP/SBPase.


J Chem Inf Model


Sun Y,Zhang R,Li D,Feng L,Wu D,Feng L,Huang P,Ren Y,Feng J,Xiao S,Wan J




Has Abstract


2014-03-24 00:00:00












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    authors: Schwaighofer A,Schroeter T,Mika S,Hansen K,Ter Laak A,Lienau P,Reichel A,Heinrich N,Müller KR

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    authors: Musmuca I,Caroli A,Mai A,Kaushik-Basu N,Arora P,Ragno R

    更新日期:2010-04-26 00:00:00

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    authors: Mollica L,Conti G,Pollegioni L,Cavalli A,Rosini E

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    authors: Chirico N,Gramatica P

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    authors: Cortes-Ciriano I,Bender A

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    authors: Jain A,Sankararamakrishnan R

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    authors: Perez C,Soler D,Soliva R,Guallar V

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    authors: Dell'Orco D,Seeber M,De Benedetti PG,Fanelli F

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    更新日期:2010-04-26 00:00:00

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    authors: Fourches D,Muratov E,Tropsha A

    更新日期:2016-07-25 00:00:00

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    authors: Cosconati S,Marinelli L,Di Leva FS,La Pietra V,De Simone A,Mancini F,Andrisano V,Novellino E,Goodsell DS,Olson AJ

    更新日期:2012-10-22 00:00:00

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    pub_type: 杂志文章


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    更新日期:2019-06-24 00:00:00

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    pub_type: 杂志文章


    authors: Borkotoky S,Dey D,Banerjee M

    更新日期:2021-01-25 00:00:00

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    pub_type: 杂志文章


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    更新日期:2019-03-25 00:00:00

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    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Setny P,Trylska J

    更新日期:2009-02-01 00:00:00

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    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Voigt JH,Elkin C,Madison VS,Duca JS

    更新日期:2008-03-01 00:00:00