Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases
Lipases/acyltransferases, such as CpLIP2 from Candida parapsilosis and CduLAc from Candida dubliniensis catalyze preferentially acyltransfer over hydrolysis when a suitable nucleophile is present, even in medium with a high thermodynamic activity of water (aW). They are related to CAL‐A from Moeszio...
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ftunivnantes:oai:HAL:hal-01918036v1 2023-05-15T13:46:10+02:00 Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases Jan-Deniau, Anne Hélène Subileau, Maeva Dubreucq, Eric Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE) Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro) 2018 https://hal.science/hal-01918036 https://doi.org/10.1002/cbic.201800279 en eng HAL CCSD Wiley-VCH Verlag info:eu-repo/semantics/altIdentifier/doi/10.1002/cbic.201800279 hal-01918036 https://hal.science/hal-01918036 doi:10.1002/cbic.201800279 PRODINRA: 443574 WOS: 000443557100008 ISSN: 1439-4227 EISSN: 1439-7633 ChemBioChem https://hal.science/hal-01918036 ChemBioChem, 2018, 19 (17), pp.1839-1844. ⟨10.1002/cbic.201800279⟩ Acyltransfer Nucleophile binding site Aqueous medium molecular structure structure function relationship acyltransférase structure moléculaire transesterification lipase relation structure fonction [SDV.IDA]Life Sciences [q-bio]/Food engineering info:eu-repo/semantics/article Journal articles 2018 ftunivnantes https://doi.org/10.1002/cbic.201800279 2023-03-01T04:55:57Z Lipases/acyltransferases, such as CpLIP2 from Candida parapsilosis and CduLAc from Candida dubliniensis catalyze preferentially acyltransfer over hydrolysis when a suitable nucleophile is present, even in medium with a high thermodynamic activity of water (aW). They are related to CAL‐A from Moesziomyces antarcticus, which in comparison displays a lower acyltransfer ability. The 3D structures of wild‐types and mutants of CAL‐A, CpLIP2 and CduLAc revealed differences in size and hydrophobicity of a large pocket located under the catalytic triad. The kinetic behavior of site‐directed mutants confirmed the role of this pocket in the competition between methanol and water as the nucleophile acceptor for the deacylation step. The mutations provided a better understanding of key structural determinants for the variable levels of acyltransferase ability observed and supported the existence of a complex network of nucleophile interactions within the enzymes. The shape and size of the possible nucleophile pocket identified also suggested that multiple binding sites could exist, supporting the hypothesis of non‐overlapping leaving and accepting nucleophiles binding sites. Article in Journal/Newspaper Antarc* antarcticus Université de Nantes: HAL-UNIV-NANTES ChemBioChem 19 17 1839 1844 |
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Université de Nantes: HAL-UNIV-NANTES |
op_collection_id |
ftunivnantes |
language |
English |
topic |
Acyltransfer Nucleophile binding site Aqueous medium molecular structure structure function relationship acyltransférase structure moléculaire transesterification lipase relation structure fonction [SDV.IDA]Life Sciences [q-bio]/Food engineering |
spellingShingle |
Acyltransfer Nucleophile binding site Aqueous medium molecular structure structure function relationship acyltransférase structure moléculaire transesterification lipase relation structure fonction [SDV.IDA]Life Sciences [q-bio]/Food engineering Jan-Deniau, Anne Hélène Subileau, Maeva Dubreucq, Eric Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases |
topic_facet |
Acyltransfer Nucleophile binding site Aqueous medium molecular structure structure function relationship acyltransférase structure moléculaire transesterification lipase relation structure fonction [SDV.IDA]Life Sciences [q-bio]/Food engineering |
description |
Lipases/acyltransferases, such as CpLIP2 from Candida parapsilosis and CduLAc from Candida dubliniensis catalyze preferentially acyltransfer over hydrolysis when a suitable nucleophile is present, even in medium with a high thermodynamic activity of water (aW). They are related to CAL‐A from Moesziomyces antarcticus, which in comparison displays a lower acyltransfer ability. The 3D structures of wild‐types and mutants of CAL‐A, CpLIP2 and CduLAc revealed differences in size and hydrophobicity of a large pocket located under the catalytic triad. The kinetic behavior of site‐directed mutants confirmed the role of this pocket in the competition between methanol and water as the nucleophile acceptor for the deacylation step. The mutations provided a better understanding of key structural determinants for the variable levels of acyltransferase ability observed and supported the existence of a complex network of nucleophile interactions within the enzymes. The shape and size of the possible nucleophile pocket identified also suggested that multiple binding sites could exist, supporting the hypothesis of non‐overlapping leaving and accepting nucleophiles binding sites. |
author2 |
Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE) Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro) |
format |
Article in Journal/Newspaper |
author |
Jan-Deniau, Anne Hélène Subileau, Maeva Dubreucq, Eric |
author_facet |
Jan-Deniau, Anne Hélène Subileau, Maeva Dubreucq, Eric |
author_sort |
Jan-Deniau, Anne Hélène |
title |
Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases |
title_short |
Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases |
title_full |
Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases |
title_fullStr |
Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases |
title_full_unstemmed |
Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in Lipases/Acyltransferases |
title_sort |
characterization and reshaping of a large and hydrophobic nucleophile pocket in lipases/acyltransferases |
publisher |
HAL CCSD |
publishDate |
2018 |
url |
https://hal.science/hal-01918036 https://doi.org/10.1002/cbic.201800279 |
genre |
Antarc* antarcticus |
genre_facet |
Antarc* antarcticus |
op_source |
ISSN: 1439-4227 EISSN: 1439-7633 ChemBioChem https://hal.science/hal-01918036 ChemBioChem, 2018, 19 (17), pp.1839-1844. ⟨10.1002/cbic.201800279⟩ |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.1002/cbic.201800279 hal-01918036 https://hal.science/hal-01918036 doi:10.1002/cbic.201800279 PRODINRA: 443574 WOS: 000443557100008 |
op_doi |
https://doi.org/10.1002/cbic.201800279 |
container_title |
ChemBioChem |
container_volume |
19 |
container_issue |
17 |
container_start_page |
1839 |
op_container_end_page |
1844 |
_version_ |
1766237958163136512 |