title: Comparative binding energy COMBINE analysis for understanding the binding determinants of type II dehydroquinase inhibitors.
abstract: Herein we report comparative binding energy (COMBINE) analyses to derive quantitative structure-activity relationship (QSAR) models that help rationalize the determinants of binding affinity for inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway. Independent COMBINE models were derived for Helicobacter pylori and Mycobacterium tuberculosis DHQ2, which is an essential enzyme in both these pathogenic bacteria that has no counterpart in human cells. These studies quantify the importance of the hydrogen bonding interactions between the ligands and the water molecule involved in the DHQ2 reaction mechanism. They also highlight important differences in the ligand interactions with the interface pocket close to the active site that could provide guides for future inhibitor design.
authors: Centro Singular de Investigación en Química Biológica y Materiales, Moleculares CIQUS, Universidad de Santiago de Compostela calle Jenaro de la Fuente s/n, 15782 Santiago de Compostela Spain.
authors: Antonio
authors: A
authors: Peón
authors: Claire
authors: C
authors: Coderch
authors: Federico
authors: F
authors: Gago
authors: Concepción
authors: C
authors: González-Bello
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000201:enzymology; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D006836:Hydro-Lyases; C020000:3-dehydroquinate dehydratase