Literature DB >> 28081610

The Bare Essentials of Antibiotic Target Validation.

Lizbeth Hedstrom1.   

Abstract

The convergence of competitive fitness experiments and phenotypic screening would seem to be an auspicious beginning for validation of an antibacterial target. IMPDH was already identified an essential protein in Mycobacterium tuberculosis when not one, but two, groups discovered inhibitors with promising antitubercular activity. A new target appeared to be born. Surprisingly, the two groups came to completely different conclusions about the vulnerability of IMPDH and its future as a drug target. This viewpoint discusses these papers and how to resolve this conundrum.

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Year:  2016        PMID: 28081610      PMCID: PMC5520969          DOI: 10.1021/acsinfecdis.6b00185

Source DB:  PubMed          Journal:  ACS Infect Dis        ISSN: 2373-8227            Impact factor:   5.084


  10 in total

1.  Metabolic enzyme IMPDH is also a transcription factor regulated by cellular state.

Authors:  Elena N Kozhevnikova; Jan A van der Knaap; Alexey V Pindyurin; Zeliha Ozgur; Wilfred F J van Ijcken; Yuri M Moshkin; C Peter Verrijzer
Journal:  Mol Cell       Date:  2012-05-31       Impact factor: 17.970

Review 2.  IMP dehydrogenase: structure, mechanism, and inhibition.

Authors:  Lizbeth Hedstrom
Journal:  Chem Rev       Date:  2009-07       Impact factor: 60.622

3.  Absolute quantitation of intracellular metabolite concentrations by an isotope ratio-based approach.

Authors:  Bryson D Bennett; Jie Yuan; Elizabeth H Kimball; Joshua D Rabinowitz
Journal:  Nat Protoc       Date:  2008       Impact factor: 13.491

4.  General and condition-specific essential functions of Pseudomonas aeruginosa.

Authors:  Samuel A Lee; Larry A Gallagher; Metawee Thongdee; Benjamin J Staudinger; Soyeon Lippman; Pradeep K Singh; Colin Manoil
Journal:  Proc Natl Acad Sci U S A       Date:  2015-04-06       Impact factor: 11.205

5.  MgATP regulates allostery and fiber formation in IMPDHs.

Authors:  Gilles Labesse; Thomas Alexandre; Laurène Vaupré; Isabelle Salard-Arnaud; Joséphine Lai Kee Him; Bertrand Raynal; Patrick Bron; Hélène Munier-Lehmann
Journal:  Structure       Date:  2013-05-02       Impact factor: 5.006

6.  The CBS subdomain of inosine 5'-monophosphate dehydrogenase regulates purine nucleotide turnover.

Authors:  Maxim Pimkin; George D Markham
Journal:  Mol Microbiol       Date:  2008-02-26       Impact factor: 3.501

7.  Genes required for mycobacterial growth defined by high density mutagenesis.

Authors:  Christopher M Sassetti; Dana H Boyd; Eric J Rubin
Journal:  Mol Microbiol       Date:  2003-04       Impact factor: 3.501

8.  Essential but Not Vulnerable: Indazole Sulfonamides Targeting Inosine Monophosphate Dehydrogenase as Potential Leads against Mycobacterium tuberculosis.

Authors:  Yumi Park; Angela Pacitto; Tracy Bayliss; Laura A T Cleghorn; Zhe Wang; Travis Hartman; Kriti Arora; Thomas R Ioerger; Jim Sacchettini; Menico Rizzi; Stefano Donini; Tom L Blundell; David B Ascher; Kyu Rhee; Ardala Breda; Nian Zhou; Veronique Dartois; Surendranadha Reddy Jonnala; Laura E Via; Valerie Mizrahi; Ola Epemolu; Laste Stojanovski; Fred Simeons; Maria Osuna-Cabello; Lucy Ellis; Claire J MacKenzie; Alasdair R C Smith; Susan H Davis; Dinakaran Murugesan; Kirsteen I Buchanan; Penelope A Turner; Margaret Huggett; Fabio Zuccotto; Maria Jose Rebollo-Lopez; Maria Jose Lafuente-Monasterio; Olalla Sanz; Gracia Santos Diaz; Joël Lelièvre; Lluis Ballell; Carolyn Selenski; Matthew Axtman; Sonja Ghidelli-Disse; Hannah Pflaumer; Markus Bösche; Gerard Drewes; Gail M Freiberg; Matthew D Kurnick; Myron Srikumaran; Dale J Kempf; Simon R Green; Peter C Ray; Kevin Read; Paul Wyatt; Clifton E Barry; Helena I Boshoff
Journal:  ACS Infect Dis       Date:  2016-10-17       Impact factor: 5.084

9.  Genes contributing to Staphylococcus aureus fitness in abscess- and infection-related ecologies.

Authors:  Michael D Valentino; Lucy Foulston; Ama Sadaka; Veronica N Kos; Regis A Villet; John Santa Maria; David W Lazinski; Andrew Camilli; Suzanne Walker; David C Hooper; Michael S Gilmore
Journal:  mBio       Date:  2014-09-02       Impact factor: 7.867

10.  The Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug Target for Tuberculosis.

Authors:  Vinayak Singh; Stefano Donini; Angela Pacitto; Claudia Sala; Ruben C Hartkoorn; Neeraj Dhar; Gyorgy Keri; David B Ascher; Guillaume Mondésert; Anthony Vocat; Andréanne Lupien; Raphael Sommer; Hélène Vermet; Sophie Lagrange; Joe Buechler; Digby F Warner; John D McKinney; Janos Pato; Stewart T Cole; Tom L Blundell; Menico Rizzi; Valerie Mizrahi
Journal:  ACS Infect Dis       Date:  2016-09-08       Impact factor: 5.084

  10 in total
  5 in total

Review 1.  Compartmentalization and regulation of GTP in control of cellular phenotypes.

Authors:  David W Wolff; Anna Bianchi-Smiraglia; Mikhail A Nikiforov
Journal:  Trends Mol Med       Date:  2022-06-16       Impact factor: 15.272

2.  The Enzymatic Activity of Inosine 5'-Monophosphate Dehydrogenase May Not Be a Vulnerable Target for Staphylococcus aureus Infections.

Authors:  Gyan Modi; Gary M Marqus; Mohana Rao Vippila; Deviprasad R Gollapalli; Youngchang Kim; Adhar C Manna; Shibin Chacko; Natalia Maltseva; Xingyou Wang; Ryan T Cullinane; Yubo Zhang; Judy L M Kotler; Petr Kuzmic; Minjia Zhang; Ann P Lawson; Andrzej Joachimiak; Ambrose Cheung; Barry B Snider; David M Rothstein; Gregory D Cuny; Lizbeth Hedstrom
Journal:  ACS Infect Dis       Date:  2021-09-30       Impact factor: 5.578

3.  Expanding Benzoxazole-Based Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitor Structure-Activity As Potential Antituberculosis Agents.

Authors:  Shibin Chacko; Helena I M Boshoff; Vinayak Singh; Davide M Ferraris; Deviprasad R Gollapalli; Minjia Zhang; Ann P Lawson; Michael J Pepi; Andrzej Joachimiak; Menico Rizzi; Valerie Mizrahi; Gregory D Cuny; Lizbeth Hedstrom
Journal:  J Med Chem       Date:  2018-05-30       Impact factor: 7.446

4.  Fragment-Based Approach to Targeting Inosine-5'-monophosphate Dehydrogenase (IMPDH) from Mycobacterium tuberculosis.

Authors:  Ana Trapero; Angela Pacitto; Vinayak Singh; Mohamad Sabbah; Anthony G Coyne; Valerie Mizrahi; Tom L Blundell; David B Ascher; Chris Abell
Journal:  J Med Chem       Date:  2018-03-23       Impact factor: 7.446

5.  Synthesis and Structure-Activity relationship of 1-(5-isoquinolinesulfonyl)piperazine analogues as inhibitors of Mycobacterium tuberculosis IMPDH.

Authors:  Vinayak Singh; Angela Pacitto; Stefano Donini; Davide M Ferraris; Sándor Boros; Eszter Illyés; Bálint Szokol; Menico Rizzi; Tom L Blundell; David B Ascher; Janos Pato; Valerie Mizrahi
Journal:  Eur J Med Chem       Date:  2019-04-15       Impact factor: 6.514

  5 in total

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