Cargando…

Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site

Pyruvate phosphate dikinase (PPDK) is an essential enzyme of C(4) photosynthesis in plants, catalyzing the ATP-driven conversion of pyruvate to phosphoenolpyruvate (PEP). It is further used by some bacteria and unicellular protists in the reverse, ATP-forming direction. Many weed species use C(4) ph...

Descripción completa

Detalles Bibliográficos
Autores principales: Minges, Alexander, Groth, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507339/
https://www.ncbi.nlm.nih.gov/pubmed/28700696
http://dx.doi.org/10.1371/journal.pone.0181139
_version_ 1783249720955633664
author Minges, Alexander
Groth, Georg
author_facet Minges, Alexander
Groth, Georg
author_sort Minges, Alexander
collection PubMed
description Pyruvate phosphate dikinase (PPDK) is an essential enzyme of C(4) photosynthesis in plants, catalyzing the ATP-driven conversion of pyruvate to phosphoenolpyruvate (PEP). It is further used by some bacteria and unicellular protists in the reverse, ATP-forming direction. Many weed species use C(4) photosynthesis in contrast to world’s major crops, which are C(3) plants. Hence inhibitors of PPDK may be used as C(4)-specific herbicides. By screening a library of 80 commercially available kinase inhibitors, we identified compounds derived from bisindolylmaleimide (bisindolylmaleimide IV, IC(50) = 0.76 ± 0.13 μM) and indirubin (indirubin-3’-monoxime, IC(50) = 4.2 ± 0.9 μM) that showed high inhibitory potency towards PPDK and are among the most effective PPDK inhibitors described today. Physiological studies on leaf tissues of a C(4) model plant confirmed in vivo inhibition of C(4)-driven photosynthesis by these substances. Moreover, comparative docking studies of non-inhibitory bisindolylmaleimide derivatives suggest that the selectivity towards PPDK may be increased by addition of functional groups to the core structure.
format Online
Article
Text
id pubmed-5507339
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-55073392017-07-25 Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site Minges, Alexander Groth, Georg PLoS One Research Article Pyruvate phosphate dikinase (PPDK) is an essential enzyme of C(4) photosynthesis in plants, catalyzing the ATP-driven conversion of pyruvate to phosphoenolpyruvate (PEP). It is further used by some bacteria and unicellular protists in the reverse, ATP-forming direction. Many weed species use C(4) photosynthesis in contrast to world’s major crops, which are C(3) plants. Hence inhibitors of PPDK may be used as C(4)-specific herbicides. By screening a library of 80 commercially available kinase inhibitors, we identified compounds derived from bisindolylmaleimide (bisindolylmaleimide IV, IC(50) = 0.76 ± 0.13 μM) and indirubin (indirubin-3’-monoxime, IC(50) = 4.2 ± 0.9 μM) that showed high inhibitory potency towards PPDK and are among the most effective PPDK inhibitors described today. Physiological studies on leaf tissues of a C(4) model plant confirmed in vivo inhibition of C(4)-driven photosynthesis by these substances. Moreover, comparative docking studies of non-inhibitory bisindolylmaleimide derivatives suggest that the selectivity towards PPDK may be increased by addition of functional groups to the core structure. Public Library of Science 2017-07-10 /pmc/articles/PMC5507339/ /pubmed/28700696 http://dx.doi.org/10.1371/journal.pone.0181139 Text en © 2017 Minges, Groth http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Minges, Alexander
Groth, Georg
Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site
title Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site
title_full Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site
title_fullStr Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site
title_full_unstemmed Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site
title_short Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site
title_sort small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507339/
https://www.ncbi.nlm.nih.gov/pubmed/28700696
http://dx.doi.org/10.1371/journal.pone.0181139
work_keys_str_mv AT mingesalexander smallmoleculeinhibitionofpyruvatephosphatedikinasetargetingthenucleotidebindingsite
AT grothgeorg smallmoleculeinhibitionofpyruvatephosphatedikinasetargetingthenucleotidebindingsite