title: Specific chemical modification of bacterial type I dehydroquinase--opportunities for drug discovery.
abstract: Type I dehydroquinase (DHQ1) is a class I aldolase enzyme that catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid by multistep mechanism that involves the formation of Schiff-base species. DHQ1 is present in plants and several bacterial sources but it does not have any counterpart in human cells. It has been suggested that DHQ1 may act as a virulence factor in vivo and therefore a promising target in the search for new antivirulence agents to combat widespread antibiotic resistance. This review covers recent progress in the structure-based design and chemical modifications caused by selective irreversible inhibitors. Computational studies aimed at understanding the experimentally obtained covalent modifications and inhibitory potencies of these inhibitors are also described.
authors.affiliation: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, calle Jenaro de la Fuente s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: González-Bello
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000201:enzymology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000502:physiology; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006836:Hydro-Lyases; C020000:3-dehydroquinate dehydratase
keywords: molecular dynamics simulations; nucleophilic catalysis; virulence