title: The crystal structures of Zea mays and Arabidopsis 4-hydroxyphenylpyruvate dioxygenase.
abstract: The transformation of 4-hydroxyphenylpyruvate to homogentisate, catalyzed by 4-hydroxyphenylpyruvate dioxygenase (HPPD), plays an important role in degrading aromatic amino acids. As the reaction product homogentisate serves as aromatic precursor for prenylquinone synthesis in plants, the enzyme is an interesting target for herbicides. In this study we report the first x-ray structures of the plant HPPDs of Zea mays and Arabidopsis in their substrate-free form at 2.0 A and 3.0 A resolution, respectively. Previous biochemical characterizations have demonstrated that eukaryotic enzymes behave as homodimers in contrast to prokaryotic HPPDs, which are homotetramers. Plant and bacterial enzymes share the overall fold but use orthogonal surfaces for oligomerization. In addition, comparison of both structures provides direct evidence that the C-terminal helix gates substrate access to the active site around a nonheme ferrous iron center. In the Z. mays HPPD structure this helix packs into the active site, sequestering it completely from the solvent. In contrast, in the Arabidopsis structure this helix tilted by about 60 degrees into the solvent and leaves the active site fully accessible. By elucidating the structure of plant HPPD enzymes we aim to provide a structural basis for the development of new herbicides.
authors.affiliation: Max-Planck-Institut für Biochemie, Abteilung für Strukturforschung, 82152 Martinsried, Germany. fritze@biochem.mpg.de
authors.forename: Iris M
authors.initials: IM
authors.lastname: Fritze
authors.forename: Lars
authors.initials: L
authors.lastname: Linden
authors.forename: Jörg
authors.initials: J
authors.lastname: Freigang
authors.forename: Günter
authors.initials: G
authors.lastname: Auerbach
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
authors.forename: Stefan
authors.initials: S
authors.lastname: Steinbacher
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D018506:Gene Expression Regulation, Plant; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D003313:Zea mays / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D018076:DNA, Complementary; D010940:Plant Proteins; D015111:4-Hydroxyphenylpyruvate Dioxygenase