Literature DB >> 23856326

Druggability of the enzymes of the non-mevalonate-pathway.

Tiziana Masini1, Blijke S Kroezen, Anna K H Hirsch.   

Abstract

The non-mevalonate pathway constitutes a source of novel drug targets. This biosynthetic route is essential for pathogens but is absent in humans. Our systematic evaluation of the druggability of all enzymes provides a convenient way of selecting targets that should be most easily inhibited by small-molecule drugs. We found that not every target is equally druggable and we identified novel, druggable, potentially allosteric sites. These results should accelerate the development of anti-infective drugs with a novel mode of action, which are needed ever more urgently in light of the rapid emergence of drug-resistant strains.
Copyright © 2013 Elsevier Ltd. All rights reserved.

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Year:  2013        PMID: 23856326     DOI: 10.1016/j.drudis.2013.07.003

Source DB:  PubMed          Journal:  Drug Discov Today        ISSN: 1359-6446            Impact factor:   7.851


  17 in total

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Authors:  Xu Wang; Rachel L Edwards; Haley Ball; Claire Johnson; Amanda Haymond; Misgina Girma; Michelle Manikkam; Robert C Brothers; Kyle T McKay; Stacy D Arnett; Damon M Osbourn; Sophie Alvarez; Helena I Boshoff; Marvin J Meyers; Robin D Couch; Audrey R Odom John; Cynthia S Dowd
Journal:  J Med Chem       Date:  2018-09-24       Impact factor: 7.446

2.  A high-throughput screening campaign to identify inhibitors of DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD).

Authors:  Amanda Haymond; Tyrone Dowdy; Chinchu Johny; Claire Johnson; Haley Ball; Allyson Dailey; Brandon Schweibenz; Karen Villarroel; Richard Young; Clark J Mantooth; Trishal Patel; Jessica Bases; Cynthia S Dowd; Robin D Couch
Journal:  Anal Biochem       Date:  2017-11-24       Impact factor: 3.365

3.  Synthesis and Evaluation of Fluoroalkyl Phosphonyl Analogues of 2- C-Methylerythritol Phosphate as Substrates and Inhibitors of IspD from Human Pathogens.

Authors:  David Bartee; Michael J Wheadon; Caren L Freel Meyers
Journal:  J Org Chem       Date:  2018-06-11       Impact factor: 4.354

4.  Antibacterial Target DXP Synthase Catalyzes the Cleavage of d-Xylulose 5-Phosphate: a Study of Ketose Phosphate Binding and Ketol Transfer Reaction.

Authors:  Melanie L Johnston; Eucolona M Bonett; Alicia A DeColli; Caren L Freel Meyers
Journal:  Biochemistry       Date:  2022-08-23       Impact factor: 3.321

5.  Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis.

Authors:  Géraldine San Jose; Emily R Jackson; Amanda Haymond; Chinchu Johny; Rachel L Edwards; Xu Wang; R Carl Brothers; Emma K Edelstein; Audrey R Odom; Helena I Boshoff; Robin D Couch; Cynthia S Dowd
Journal:  ACS Infect Dis       Date:  2016-10-12       Impact factor: 5.084

6.  Antibacterial activity of 2-amino-4-hydroxypyrimidine-5-carboxylates and binding to Burkholderia pseudomallei 2-C-methyl-d-erythritol-2,4-cyclodiphosphate synthase.

Authors:  Sydney M Watkins; Debarati Ghose; Joy M Blain; Dakota L Grote; Chi-Hao Luan; Michael Clare; R Meganathan; James R Horn; Timothy J Hagen
Journal:  Bioorg Med Chem Lett       Date:  2019-09-03       Impact factor: 2.823

7.  Toward Understanding the Chemistry and Biology of 1-Deoxy-d-xylulose 5-Phosphate (DXP) Synthase: A Unique Antimicrobial Target at the Heart of Bacterial Metabolism.

Authors:  David Bartee; Caren L Freel Meyers
Journal:  Acc Chem Res       Date:  2018-09-11       Impact factor: 22.384

8.  First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization.

Authors:  Robin M Gierse; Rick Oerlemans; Eswar R Reddem; Victor O Gawriljuk; Alaa Alhayek; Dominik Baitinger; Harald Jakobi; Bernd Laber; Gudrun Lange; Anna K H Hirsch; Matthew R Groves
Journal:  Sci Rep       Date:  2022-05-04       Impact factor: 4.996

9.  PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins.

Authors:  Hiba Abi Hussein; Alexandre Borrel; Colette Geneix; Michel Petitjean; Leslie Regad; Anne-Claude Camproux
Journal:  Nucleic Acids Res       Date:  2015-05-08       Impact factor: 16.971

10.  Comparison of FDA Approved Kinase Targets to Clinical Trial Ones: Insights from Their System Profiles and Drug-Target Interaction Networks.

Authors:  Jingyu Xu; Panpan Wang; Hong Yang; Jin Zhou; Yinghong Li; Xiaoxu Li; Weiwei Xue; Chunyan Yu; Yubin Tian; Feng Zhu
Journal:  Biomed Res Int       Date:  2016-07-28       Impact factor: 3.411

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