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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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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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 |
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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 |
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