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

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 resolut...

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Autores principales:	Muzet, Nicolas, Guillot, Benoît, Jelsch, Christian, Howard, Eduardo Ignacio, Lecomte, Claude
Formato:	Articulo
Lenguaje:	Inglés
Publicado:	2003
Materias:	Ciencias Exactas electron density electrostatic potential crystallography
Acceso en línea:	http://sedici.unlp.edu.ar/handle/10915/84550
Aporte de:	SEDICI (UNLP) de Universidad Nacional de La Plata

id	I19-R120-10915-84550
record_format	dspace
institution	Universidad Nacional de La Plata
institution_str	I-19
repository_str	R-120
collection	SEDICI (UNLP)
language	Inglés
topic	Ciencias Exactas electron density electrostatic potential crystallography
spellingShingle	Ciencias Exactas electron density electrostatic potential crystallography Muzet, Nicolas Guillot, Benoît Jelsch, Christian Howard, Eduardo Ignacio Lecomte, Claude Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
topic_facet	Ciencias Exactas electron density electrostatic potential crystallography
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.
format	Articulo Articulo
author	Muzet, Nicolas Guillot, Benoît Jelsch, Christian Howard, Eduardo Ignacio Lecomte, Claude
author_facet	Muzet, Nicolas Guillot, Benoît Jelsch, Christian Howard, Eduardo Ignacio Lecomte, Claude
author_sort	Muzet, Nicolas
title	Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
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
publishDate	2003
url	http://sedici.unlp.edu.ar/handle/10915/84550
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Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

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