Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

Autores
Muzet, Nicolas; Guillot, Benoît; Jelsch, Christian; Howard, Eduardo Ignacio; Lecomte, Claude
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP+ and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.
Instituto de Física de Líquidos y Sistemas Biológicos
Facultad de Ciencias Exactas
Materia
Ciencias Exactas
electron density
electrostatic potential
crystallography
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/84550

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network_name_str SEDICI (UNLP)
spelling Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculationsMuzet, NicolasGuillot, BenoîtJelsch, ChristianHoward, Eduardo IgnacioLecomte, ClaudeCiencias Exactaselectron densityelectrostatic potentialcrystallographyThe electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP<SUP>+</SUP> and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias Exactas2003info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf8742-8747http://sedici.unlp.edu.ar/handle/10915/84550enginfo:eu-repo/semantics/altIdentifier/issn/0027-8424info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1432955100info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:16:15Zoai:sedici.unlp.edu.ar:10915/84550Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:16.098SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
title Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
spellingShingle Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
Muzet, Nicolas
Ciencias Exactas
electron density
electrostatic potential
crystallography
title_short Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
title_full Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
title_fullStr Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
title_full_unstemmed Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
title_sort Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
dc.creator.none.fl_str_mv Muzet, Nicolas
Guillot, Benoît
Jelsch, Christian
Howard, Eduardo Ignacio
Lecomte, Claude
author Muzet, Nicolas
author_facet Muzet, Nicolas
Guillot, Benoît
Jelsch, Christian
Howard, Eduardo Ignacio
Lecomte, Claude
author_role author
author2 Guillot, Benoît
Jelsch, Christian
Howard, Eduardo Ignacio
Lecomte, Claude
author2_role author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
electron density
electrostatic potential
crystallography
topic Ciencias Exactas
electron density
electrostatic potential
crystallography
dc.description.none.fl_txt_mv The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP<SUP>+</SUP> and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.
Instituto de Física de Líquidos y Sistemas Biológicos
Facultad de Ciencias Exactas
description The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP<SUP>+</SUP> and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.
publishDate 2003
dc.date.none.fl_str_mv 2003
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/84550
url http://sedici.unlp.edu.ar/handle/10915/84550
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0027-8424
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1432955100
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
8742-8747
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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