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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/84550
Ver los metadatos del registro completo
id |
SEDICI_5022ede0b270d9ffbc77312c3e99f174 |
---|---|
oai_identifier_str |
oai:sedici.unlp.edu.ar:10915/84550 |
network_acronym_str |
SEDICI |
repository_id_str |
1329 |
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 |
_version_ |
1844616035237363712 |
score |
13.070432 |