title: The prokaryotic FAD synthetase family: a potential drug target.
abstract: Disruption of cellular production of the flavin cofactors, flavin adenine mononucleotide (FMN) and flavin adenine dinucleotide(FAD) will prevent the assembly of a large number of flavoproteins and flavoenzymes involved in key metabolic processes in all types of organisms. The enzymes responsible for FMN and FAD production in prokaryotes and eukaryotes exhibit various structural characteristics to catalyze the same chemistry, a fact that converts the prokaryotic FAD synthetase (FADS) in a potential drug target for the development of inhibitors endowed with anti-pathogenic activity. The first step before searching for selective inhibitors of FADS is to understand the structural and functional mechanisms for the riboflavin kinase and FMN adenylyltransferase activities of the prokaryotic enzyme, and particularly to identify their differential functional characteristics with regard to the enzymes performing similar functions in other organisms, particularly humans. In this paper, an overview of the current knowledge of the structure-function relationships in prokaryotic FADS has been presented, as well as of the state of the art in the use of these enzymes as drug targets.
authors.affiliation: Department of Biochemistry, and Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Serrano
authors.forename: Patricia
authors.initials: P
authors.lastname: Ferreira
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez-Júlvez
authors.forename: Milagros
authors.initials: M
authors.lastname: Medina
mesh_terms: D000818:Animals; D001665:Binding Sites; D055808:Drug Discovery; D005486:Flavin Mononucleotide / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011387:Prokaryotic Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D005182:Flavin-Adenine Dinucleotide; D005486:Flavin Mononucleotide; D009713:Nucleotidyltransferases; C020143:FMN adenylyltransferase