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Molecular architectures of benzoic acid-specific type III polyketide synthases
Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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International Union of Crystallography
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713876/ https://www.ncbi.nlm.nih.gov/pubmed/29199980 http://dx.doi.org/10.1107/S2059798317016618 |
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author | Stewart, Charles Woods, Kate Macias, Greg Allan, Andrew C. Hellens, Roger P. Noel, Joseph P. |
author_facet | Stewart, Charles Woods, Kate Macias, Greg Allan, Andrew C. Hellens, Roger P. Noel, Joseph P. |
author_sort | Stewart, Charles |
collection | PubMed |
description | Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a better understanding of structure–function relationships within the type III PKS family, the crystal structures of biphenyl synthase from Malus × domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone synthase from Malus × domestica. Both biphenyl synthase and benzophenone synthase contain mutations that reshape their active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the binding of small hydrophobic substrates. The active-site cavities of biphenyl synthase and benzophenone synthase also contain a novel pocket associated with their chain-elongation and cyclization reactions. Collectively, these results illuminate structural determinants of benzoic acid-specific type III PKSs and expand the understanding of the evolution of specialized metabolic pathways in plants. |
format | Online Article Text |
id | pubmed-5713876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-57138762017-12-13 Molecular architectures of benzoic acid-specific type III polyketide synthases Stewart, Charles Woods, Kate Macias, Greg Allan, Andrew C. Hellens, Roger P. Noel, Joseph P. Acta Crystallogr D Struct Biol Research Papers Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a better understanding of structure–function relationships within the type III PKS family, the crystal structures of biphenyl synthase from Malus × domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone synthase from Malus × domestica. Both biphenyl synthase and benzophenone synthase contain mutations that reshape their active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the binding of small hydrophobic substrates. The active-site cavities of biphenyl synthase and benzophenone synthase also contain a novel pocket associated with their chain-elongation and cyclization reactions. Collectively, these results illuminate structural determinants of benzoic acid-specific type III PKSs and expand the understanding of the evolution of specialized metabolic pathways in plants. International Union of Crystallography 2017-11-30 /pmc/articles/PMC5713876/ /pubmed/29199980 http://dx.doi.org/10.1107/S2059798317016618 Text en © Stewart et al. 2017 http://creativecommons.org/licenses/by/2.0/uk/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/2.0/uk/ |
spellingShingle | Research Papers Stewart, Charles Woods, Kate Macias, Greg Allan, Andrew C. Hellens, Roger P. Noel, Joseph P. Molecular architectures of benzoic acid-specific type III polyketide synthases |
title | Molecular architectures of benzoic acid-specific type III polyketide synthases |
title_full | Molecular architectures of benzoic acid-specific type III polyketide synthases |
title_fullStr | Molecular architectures of benzoic acid-specific type III polyketide synthases |
title_full_unstemmed | Molecular architectures of benzoic acid-specific type III polyketide synthases |
title_short | Molecular architectures of benzoic acid-specific type III polyketide synthases |
title_sort | molecular architectures of benzoic acid-specific type iii polyketide synthases |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713876/ https://www.ncbi.nlm.nih.gov/pubmed/29199980 http://dx.doi.org/10.1107/S2059798317016618 |
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