3D-QSAR, Molecular Docking and Molecular Dynamics Simulation of Pseudomonas aeruginosa LpxC Inhibitors.


:As an important target for the development of novel antibiotics, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) has been widely studied. Pyridone methylsulfone hydroxamate (PMH) compounds can effectively inhibit the catalytic activity of LpxC. In this work, the three-dimensional quantitative structure-activity relationships of PMH inhibitors were explored and models with good predictive ability were established using comparative molecular field analysis and comparative molecular similarity index analysis methods. The effect of PMH inhibitors' electrostatic potential on the inhibitory ability of Pseudomonas aeruginosa LpxC (PaLpxC) is revealed at the molecular level via molecular electrostatic potential analyses. Then, two molecular dynamics simulations for the PaLpxC and PaLpxC-inhibitor systems were also performed respectively to investigate the key residues of PaLpxC hydrolase binding to water molecules. The results indicate that orderly alternative water molecules can form stable hydrogen bonds with M62, E77, T190, and H264 in the catalytic center, and tetracoordinate to zinc ion along with H78, H237, and D241. It was found that the conformational transition space of PaLpxC changes after association with PMH inhibitors through free energy landscape and cluster analyses. Finally, a possible inhibitory mechanism of PMH inhibitors was proposed, based on our molecular simulation. This paper will provide a theoretical basis for the molecular design of LpxC-targeting antibiotics.


Int J Mol Sci


Zuo K,Liang L,Du W,Sun X,Liu W,Gou X,Wan H,Hu J




Has Abstract


2017-05-06 00:00:00










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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Luan H,Liao W,Niu H,Cui X,Chen X,Zhi H

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  • LGM2605 Reduces Space Radiation-Induced NLRP3 Inflammasome Activation and Damage in In Vitro Lung Vascular Networks.

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Chatterjee S,Pietrofesa RA,Park K,Tao JQ,Carabe-Fernandez A,Berman AT,Koumenis C,Sielecki T,Christofidou-Solomidou M

    更新日期:2019-01-05 00:00:00

  • The Light and Dark Sides of Virtual Screening: What Is There to Know?

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Gimeno A,Ojeda-Montes MJ,Tomás-Hernández S,Cereto-Massagué A,Beltrán-Debón R,Mulero M,Pujadas G,Garcia-Vallvé S

    更新日期:2019-03-19 00:00:00

  • Proteomic Biomarkers of Retinal Inflammation in Diabetic Retinopathy.

    abstract::Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of prolonged hyperglycemia and is characterized by leaky retinal vasculature, retinal ischemia, retinal inflammation, angiogenesis, and neovascularization. Th...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Youngblood H,Robinson R,Sharma A,Sharma S

    更新日期:2019-09-25 00:00:00

  • Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Gitto S,Villa E

    更新日期:2016-04-02 00:00:00

  • Effect of Pulsed Electric Field on Membrane Lipids and Oxidative Injury of Salmonella typhimurium.

    abstract::Salmonella typhimurium cells were subjected to pulsed electric field (PEF) treatment at 25 kV/cm for 0-4 ms to investigate the effect of PEF on the cytoplasmic membrane lipids and oxidative injury of cells. Results indicated that PEF treatment induced a decrease of membrane fluidity of Salmonella typhimurium (S. typhi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


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    更新日期:2016-08-22 00:00:00

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    journal_title:International journal of molecular sciences

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    authors: Park TM,Kang D,Jang I,Yun WS,Shim JH,Jeong YH,Kwak JY,Yoon S,Jin S

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  • Chaperone-E3 Ligase Complex HSP70-CHIP Mediates Ubiquitination of Ribosomal Protein S3.

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    journal_title:International journal of molecular sciences

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    authors: Hwang I,Cho SW,Ahn JY

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    journal_title:International journal of molecular sciences

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    authors: Kolmas J,Sobczak M,Olędzka E,Nałęcz-Jawecki G,Dębek C

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    journal_title:International journal of molecular sciences

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    authors: Haarmann A,Schuhmann MK,Silwedel C,Monoranu CM,Stoll G,Buttmann M

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    authors: Wiciński M,Domanowska A,Wódkiewicz E,Malinowski B

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    authors: Fry LE,Peddle CF,Barnard AR,McClements ME,MacLaren RE

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    journal_title:International journal of molecular sciences

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    authors: Lin KJ,Lin KL,Chen SD,Liou CW,Chuang YC,Lin HY,Lin TK

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    journal_title:International journal of molecular sciences

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    authors: Jiang C,Nischal H,Sun H,Li L,Cao Y,Wei P,Chang JY,Teng BB

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    journal_title:International journal of molecular sciences

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    journal_title:International journal of molecular sciences

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    authors: Fefilova A,Melnikov P,Prikazchikova T,Abakumova T,Kurochkin I,Mazin PV,Ziganshin R,Sergeeva O,Zatsepin TS

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    pub_type: 杂志文章,评审


    authors: Körtvelyessy P,Huchtemann T,Heinze HJ,Bittner DM

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    authors: Osman OI,Alyoubi AO,Elroby SA,Hilal RH,Aziz SG

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    journal_title:International journal of molecular sciences

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


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    journal_title:International journal of molecular sciences

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    authors: Lkhagvadorj K,Zeng Z,Meyer KF,Verweij LP,Kooistra W,Reinders-Luinge M,Dijkhuizen HW,de Graaf IAM,Plösch T,Hylkema MN

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    journal_title:International journal of molecular sciences

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    authors: Wang Y,de Boer R,Vischer N,van Haastrecht P,Setlow P,Brul S

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  • Reply to the Letter to the Editor by Li et al.: Bioinformatics Analysis in Mice with Diet-Induced Nonalcoholic Steatohepatitis Treated with Astaxanthin and Vitamin E.

    abstract::n/a. ...

    journal_title:International journal of molecular sciences

    pub_type: 评论,杂志文章


    authors: Kobori M,Takahashi Y,Sakurai M,Ni Y,Chen G,Nagashimada M,Kaneko S,Ota T

    更新日期:2017-05-05 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Guadagni S,Clementi M,Masedu F,Fiorentini G,Sarti D,Deraco M,Kusamura S,Papasotiriou I,Apostolou P,Aigner KR,Zavattieri G,Farina AR,Vizzielli G,Scambia G,Mackay AR

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Pechanova O,Pechan T

    更新日期:2015-11-30 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Smolikova G,Dolgikh E,Vikhnina M,Frolov A,Medvedev S

    更新日期:2017-09-16 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Wysocka M,Romanowska A,Gruba N,Michalska M,Giełdoń A,Lesner A

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Yan AF,Chen T,Chen S,Ren CH,Hu CQ,Cai YM,Liu F,Tang DS

    更新日期:2016-05-30 00:00:00

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    abstract::Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine for treating peptic ulcers and inflammatory problems. In this context, this study aims to characterize the chemical constituents and evaluate the gastroprotective activity of the leaf juices of the two species in acute gastri...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: de Araújo ERD,Guerra GCB,Araújo DFS,de Araújo AA,Fernandes JM,de Araújo Júnior RF,da Silva VC,de Carvalho TG,Ferreira LS,Zucolotto SM

    更新日期:2018-04-24 00:00:00