title: Modeling iron-catecholates binding to NGAL protein.
abstract: Neutrophil gelatinase associated lipocalin (NGAL) protein is attracting a great interest because of its antibacterial properties played upon modulating iron content in competition against iron acquisition processes developed by pathogenic bacteria that bind selective ferric iron chelators (siderophores). Besides its known high affinity to enterobactin, the most important siderophore, it has been recently shown that NGAL is able to bind Fe(III) coordinated by catechols. The selective binding of Fe(III)-catechol ligands to NGAL is here studied by using iron coordination structures with one, two, and three catecholate ligands. By means of a computational approach that consists of B3LYP/6-311G(d,p) quantum calculations for geometries, electron properties and electrostatic potentials of ligands, protein-ligand flexible docking calculations, analyses of protein-ligand interfaces, and Poisson-Boltzmann electrostatic potentials for proteins, we study the binding of iron catecholate ligands to NGAL as a central member of the lipocalin family of proteins. This approach provides a modeling basis for exploring in silico the selective binding of iron catecholates ligands giving a detailed picture of their interactions in terms of electrostatic effects and a network of hydrogen bonds in the protein binding pocket.
authors.affiliation: Centro de Biotecnología y Genómica de Plantas (CBGP), Campus de Montegancedo, Universidad Politécnica de Madrid (UPM), 28223 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gómez-Casado
authors.forename: Franziska
authors.initials: F
authors.lastname: Roth-Walter
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
authors.forename: Araceli
authors.initials: A
authors.lastname: Díaz-Perales
authors.forename: Luis F
authors.initials: LF
authors.lastname: Pacios
mesh_terms: D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D054834:Lipocalins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D055672:Static Electricity
chemical_list: D005290:Ferric Compounds; D008024:Ligands; D054834:Lipocalins; D007501:Iron
keywords: Catechols; Electrostatic potential; Iron chelators; Lipocalins; Protein–ligand docking; Protein–ligand interfaces