title: Crystal structure of a minimal nitroreductase, ydjA, from Escherichia coli K12 with and without FMN cofactor.
abstract: Nitroreductases (NTR) are enzymes that reduce hazardous nitroaromatic compounds and are of special interest due to their potential use in bioremediation and their activation of prodrugs in directed anticancer therapies. We elucidated the crystal structures of ydjA from Escherichia coli (Ec_ydjA), one of the smallest NTRs, in its flavin mononucleotide (FMN)-bound and cofactor-free forms. The alpha+beta mixed monomeric Ec_ydjA forms a homodimeric structure through the interactions of the long central helices and the extended regions at both termini. Two FMN molecules are bound at the dimeric interface. The absence of the 30 internal amino acids in Ec_ydjA, which forms two helices and restricts the cofactor and substrate binding in other NTR family members, creates a wider and more flexible active site. Unlike the bent FMN ring structures present in most NTR complexes currently known, the flavin system in the Ec_ydjA structure maintains a flat ring conformation, which is sandwiched between a Trp and a His residue from each monomer. The analysis of our Ec_ydjA structure explains its specificity for larger substrates and provides structural information for the rational design of novel prodrugs with the ability to reduce nitrogen-containing hazardous molecules.
authors.affiliation: Department of Chemistry and Institute of Basic Sciences, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Ji-Woo
authors.initials: JW
authors.lastname: Choi
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nishi
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Che-Hun
authors.initials: CH
authors.lastname: Jung
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D048168:Escherichia coli K12 / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D005486:Flavin Mononucleotide / Q000378:metabolism*; D008969:Molecular Sequence Data; D009601:Nitroreductases / Q000737:chemistry*
chemical_list: D001051:Apoenzymes; D029968:Escherichia coli Proteins; D005486:Flavin Mononucleotide; D009601:Nitroreductases; C526139:ydjA protein, E coli