Structure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC.

  title={Structure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC.},
  author={June M. Brownlee and Kayunta Johnson‐Winters and David H. T. Harrison and Graham R. Moran},
  volume={43 21},
Di- and triketone inhibitors of (4-hydroxyphenyl)pyruvate dioxygenase (HPPD) are both effective herbicides and therapeutics. The inhibitory activity is used to halt the production of lipophilic redox cofactors in plants and also in humans to prevent accumulation of toxic metabolic byproducts that arise from specific inborn defects of tyrosine catabolism. The three-dimensional structure of the Fe(II) form of HPPD from Streptomyces avermitilis in complex with the inhibitor 2-[2-nitro-4… 
Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione.
In this paper the available information concerning the molecular mechanism of HPPD inhibition by NTBC is collected, supplemented by results of additional theoretical DFT and/or MP2 calculations of the energetic effects of individual elementary molecular transformations.
The different catalytic roles of the metal-binding ligands in human 4-hydroxyphenylpyruvate dioxygenase.
Modelling the rearrangement of the co-ordination environment and the dynamic behaviour of bound dioxygen in the H266A and H183A variants suggest that the residues regulate the geometry of the reactive oxygen intermediate during the oxidation reaction.
Beta-triketone inhibitors of plant p-hydroxyphenylpyruvate dioxygenase: modeling and comparative molecular field analysis of their interactions.
Modeling of the binding of the triketones to HPPD, three-dimensional QSAR analysis using CoMFA (comparative molecular field analysis), and evaluation of the hydrophobic contribution with HINT (hydropathic interactions) provided a structural basis to describe the ligand/receptor interactions.
Toxoflavin lyase requires a novel 1-His-2-carboxylate facial triad.
High-resolution crystal structures are reported for apo, holo, and substrate-bound forms of a toxoflavin-degrading metalloenzyme (TflA), and this anionic species is predicted to be the electron source responsible for reductive activation of oxygen to produce a peroxytox oflavin intermediate.
Role of substrate positioning in the catalytic reaction of 4-hydroxyphenylpyruvate dioxygenase-A QM/MM Study.
From the computed reaction free energy profiles it follows that the most likely mechanism of 4-hydroxyphenylpyruvate dioxygenase involves electrophilic attack on the C1 carbon of the ring and subsequent single-step heterolytic migration of the substituent.
4-Hydroxyphenylpyruvate dioxygenase.
  • G. Moran
  • Biology, Chemistry
    Archives of biochemistry and biophysics
  • 2005