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

Nicolas Muzet (1) , Benoît Guillot (1) , Christian Jelsch (1) , Eduardo Howard (2, 3) , Claude Lecomte (1)

1 CRM2 - Cristallographie, Résonance Magnétique et Modélisations
2 IFLYSIB - Instituto de Física de Líquidos y Sistemas Biológicos [La Plata]
3 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

The electron density and electrostatic potential in an Aldose Reductase holoenzyme complex have been studied by DFT and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway using NADPH as a co-factor. 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 Density Functional Theory (DFT) calculations have been performed on 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with program MoPro using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids.

Domains: Structural Biology [q-bio.BM]; Cristallography

Nicolas Muzet, Benoît Guillot, Christian Jelsch, Eduardo Howard, Claude Lecomte. Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations. Proceedings of the National Academy of Sciences of the United States of America, 2011, 100 (15), pp.8742-8747. ⟨10.1073/pnas.1432955100⟩. ⟨hal-01720080⟩