title: Structures of aminophenol dioxygenase in complex with intermediate, product and inhibitor.
abstract: Dioxygen activation by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Here, crystal structures of 2-aminophenol 1,6-dioxygenase, an enzyme that represents a minor group of extradiol dioxygenases and that catalyses the ring opening of 2-aminophenol, in complex with the lactone intermediate (4Z,6Z)-3-iminooxepin-2(3H)-one and the product 2-aminomuconic 6-semialdehyde and in complex with the suicide inhibitor 4-nitrocatechol are reported. The Fe-ligand binding schemes observed in these structures revealed some common geometrical characteristics that are shared by the published structures of extradiol dioxygenases, suggesting that enzymes that catalyse the oxidation of noncatecholic compounds are very likely to utilize a similar strategy for dioxygen activation and the fission of aromatic rings as the canonical mechanism. The Fe-ligation arrangement, however, is strikingly enantiomeric to that of all other 2-His-1-carboxylate enzymes apart from protocatechuate 4,5-dioxygenase. This structural variance leads to the generation of an uncommon O(-)-Fe(2+)-O(-) species prior to O(2) binding, which probably forms the structural basis on which APD distinguishes its specific substrate and inhibitor, which share an analogous molecular structure.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: De Feng
authors.initials: de F
authors.lastname: Li
authors.forename: Jia Yue
authors.initials: JY
authors.lastname: Zhang
authors.forename: Yan Jie
authors.initials: YJ
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Hu
authors.forename: Shuang Jiang
authors.initials: SJ
authors.lastname: Liu
authors.forename: Da Cheng
authors.initials: da C
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000627:Aminophenols / Q000737:chemistry; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002396:Catechols / Q000737:chemistry* / Q000494:pharmacology*; D020585:Comamonas / Q000201:enzymology; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods; D049308:Dioxygenases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D007501:Iron / Q000737:chemistry; D000090463:Iron Deficiencies; D021122:Protein Subunits / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D000627:Aminophenols; D001426:Bacterial Proteins; D002396:Catechols; D021122:Protein Subunits; C027667:2-aminophenol; D007501:Iron; C106307:2-aminophenol 1,6-dioxygenase; D049308:Dioxygenases; C001833:4-nitrocatechol