Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism

Phenprocoumon is an oral anticoagulant used for the pro- phylaxis and treatment of disorders due to thrombosis. However, if oral anticoagulants are not metabolized, they could exacerbate and generate clotting disorders. Phenprocoumon is metabolized by at least four hepatic enzymes members of the cyt...

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Detalles Bibliográficos
Autores: Israel Quiroga, Thomas Scior
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:México
Institución:Benemérita Universidad Autónoma de Puebla
Repositorio:Redalyc-BUAP
OAI Identifier:oai:redalyc.org:47554335010
Acceso en línea:https://www.redalyc.org/articulo.oa?id=47554335010
Access Level:acceso abierto
Palabra clave:Química
CYP450
CYP2C9
Docking
Structure
Phenprocoumon
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spelling Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon MetabolismIsrael QuirogaThomas SciorQuímicaCYP450CYP2C9DockingStructurePhenprocoumonPhenprocoumon is an oral anticoagulant used for the pro- phylaxis and treatment of disorders due to thrombosis. However, if oral anticoagulants are not metabolized, they could exacerbate and generate clotting disorders. Phenprocoumon is metabolized by at least four hepatic enzymes members of the cytochromes P450 family; three of which are members of the same subfamily (CYP2C9, CYP2C19 and CYP2C8). Even with too many differences in their amino acid sequence and tertiary structures, CYP2C9 and CYP3A4 have the most similar metabolic activity on phenprocoumon. In this study, we were able to explain these activity similarities using force fields of molec - ular mechanics for geometry and energy optimization in combination with docking techniques. The results were compared to study Struc- ture-Function Relationships (SFR) of our four target proteins (CY - P2C9, CYP2C19, CYP2C8 and CYP3A4). The study and prediction of metabolism and sites of metabolisms of drugs was successfully per - formed using this approach.Sociedad Química de México2017info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdf1870-249Xhttps://www.redalyc.org/articulo.oa?id=47554335010Journal of the Mexican Chemical Society (México) Num.4 Vol.61reponame:Redalyc-BUAPinstname:Benemérita Universidad Autónoma de Pueblainstacron:BUAPenhttp://www.redalyc.org/revista.oa?id=475Journal of the Mexican Chemical Societyinfo:eu-repo/semantics/openAccessoai:redalyc.org:475543350102024-08-23T15:26:53Z
dc.title.none.fl_str_mv Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
title Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
spellingShingle Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
Israel Quiroga
Química
CYP450
CYP2C9
Docking
Structure
Phenprocoumon
title_short Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
title_full Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
title_fullStr Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
title_full_unstemmed Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
title_sort Structure-Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism
dc.creator.none.fl_str_mv Israel Quiroga
Thomas Scior
author Israel Quiroga
author_facet Israel Quiroga
Thomas Scior
author_role author
author2 Thomas Scior
author2_role author
dc.subject.none.fl_str_mv Química
CYP450
CYP2C9
Docking
Structure
Phenprocoumon
topic Química
CYP450
CYP2C9
Docking
Structure
Phenprocoumon
description Phenprocoumon is an oral anticoagulant used for the pro- phylaxis and treatment of disorders due to thrombosis. However, if oral anticoagulants are not metabolized, they could exacerbate and generate clotting disorders. Phenprocoumon is metabolized by at least four hepatic enzymes members of the cytochromes P450 family; three of which are members of the same subfamily (CYP2C9, CYP2C19 and CYP2C8). Even with too many differences in their amino acid sequence and tertiary structures, CYP2C9 and CYP3A4 have the most similar metabolic activity on phenprocoumon. In this study, we were able to explain these activity similarities using force fields of molec - ular mechanics for geometry and energy optimization in combination with docking techniques. The results were compared to study Struc- ture-Function Relationships (SFR) of our four target proteins (CY - P2C9, CYP2C19, CYP2C8 and CYP3A4). The study and prediction of metabolism and sites of metabolisms of drugs was successfully per - formed using this approach.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 1870-249X
https://www.redalyc.org/articulo.oa?id=47554335010
identifier_str_mv 1870-249X
url https://www.redalyc.org/articulo.oa?id=47554335010
dc.language.none.fl_str_mv en
language_invalid_str_mv en
dc.relation.none.fl_str_mv http://www.redalyc.org/revista.oa?id=475
dc.rights.none.fl_str_mv Journal of the Mexican Chemical Society
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Journal of the Mexican Chemical Society
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Sociedad Química de México
publisher.none.fl_str_mv Sociedad Química de México
dc.source.none.fl_str_mv Journal of the Mexican Chemical Society (México) Num.4 Vol.61
reponame:Redalyc-BUAP
instname:Benemérita Universidad Autónoma de Puebla
instacron:BUAP
instname_str Benemérita Universidad Autónoma de Puebla
instacron_str BUAP
institution BUAP
reponame_str Redalyc-BUAP
collection Redalyc-BUAP
repository.name.fl_str_mv
repository.mail.fl_str_mv
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