1w1o Citations

Structures of Michaelis and product complexes of plant cytokinin dehydrogenase: implications for flavoenzyme catalysis.

J. Mol. Biol. 341 1237-49 (2004)
Related entries: 1w1s, 1w1r, 1w1q

Cited: 26 times
EuropePMC logo PMID: 15321719

Abstract

Cytokinins form a diverse class of compounds that are essential for plant growth. Cytokinin dehydrogenase has a major role in the control of the levels of these plant hormones by catalysing their irreversible oxidation. The crystal structure of Zea mays cytokinin dehydrogenase displays the same two-domain topology of the flavoenzymes of the vanillyl-alcohol oxidase family but its active site cannot be related to that of any other family member. The X-ray analysis reveals a bipartite architecture of the catalytic centre, which consists of a funnel-shaped region on the protein surface and an internal cavity lined by the flavin ring. A pore with diameter of about 4A connects the two active-site regions. Snapshots of two critical steps along the reaction cycle were obtained through the structural analysis of the complexes with a slowly reacting substrate and the reaction product, which correspond to the states immediately before (Michaelis complex) and after (product complex) oxidation has taken place. The substrate displays a "plug-into-socket" binding mode that seals the catalytic site and precisely positions the carbon atom undergoing oxidation in close contact with the reactive locus of the flavin. A polarising H-bond between the substrate amine group and an Asp-Glu pair may facilitate oxidation. Substrate to product conversion results in small atomic movements, which lead to a planar conformation of the reaction product allowing double-bond conjugation. These features in the mechanism of amine recognition and oxidation differ from those observed in other flavin-dependent amine oxidases.

Reviews citing this publication (12)

  1. To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes. Mattevi A. Trends Biochem. Sci. 31 276-283 (2006)
  2. New insights into the biology of cytokinin degradation. Werner T, Köllmer I, Bartrina I, Holst K, Schmülling T. Plant Biol (Stuttg) 8 371-381 (2006)
  3. What's in a covalent bond? On the role and formation of covalently bound flavin cofactors. Heuts DP, Scrutton NS, McIntire WS, Fraaije MW. FEBS J. 276 3405-3427 (2009)
  4. Evolution of cytokinin biosynthesis and degradation. Frébort I, Kowalska M, Hluska T, Frébortová J, Galuszka P. J. Exp. Bot. 62 2431-2452 (2011)
  5. The growing VAO flavoprotein family. Leferink NG, Heuts DP, Fraaije MW, van Berkel WJ. Arch. Biochem. Biophys. 474 292-301 (2008)
  6. Cytokinin oxidase is key enzyme of cytokinin degradation. Avalbaev AM, Somov KA, Yuldashev RA, Shakirova FM. Biochemistry Mosc. 77 1354-1361 (2012)
  7. Cytokinin oxidase is key enzyme of cytokinin degradation. Avalbaev AM, Somov KA, Yuldashev RA, Shakirova FM. Biochemistry Mosc. 77 1354-1361 (2012)
  8. Evolution of cytokinin biosynthesis and degradation. Frébort I, Kowalska M, Hluska T, Frébortová J, Galuszka P. J. Exp. Bot. 62 2431-2452 (2011)
  9. What's in a covalent bond? On the role and formation of covalently bound flavin cofactors. Heuts DP, Scrutton NS, McIntire WS, Fraaije MW. FEBS J. 276 3405-3427 (2009)
  10. The growing VAO flavoprotein family. Leferink NG, Heuts DP, Fraaije MW, van Berkel WJ. Arch. Biochem. Biophys. 474 292-301 (2008)
  11. To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes. Mattevi A. Trends Biochem. Sci. 31 276-283 (2006)
  12. New insights into the biology of cytokinin degradation. Werner T, Köllmer I, Bartrina I, Holst K, Schmülling T. Plant Biol (Stuttg) 8 371-381 (2006)

Articles citing this publication (14)

  1. ThermoFAD, a Thermofluor-adapted flavin ad hoc detection system for protein folding and ligand binding. Forneris F, Orru R, Bonivento D, Chiarelli LR, Mattevi A. FEBS J. 276 2833-2840 (2009)
  2. A concerted mechanism for berberine bridge enzyme. Winkler A, Lyskowski A, Riedl S, Puhl M, Kutchan TM, Macheroux P, Gruber K. Nat. Chem. Biol. 4 739-741 (2008)
  3. Subcellular localization and biochemical comparison of cytosolic and secreted cytokinin dehydrogenase enzymes from maize. Smehilová M, Galuszka P, Bilyeu KD, Jaworek P, Kowalska M, Sebela M, Sedlárová M, English JT, Frébort I. J. Exp. Bot. 60 2701-2712 (2009)
  4. Structural basis for benzothiazinone-mediated killing of Mycobacterium tuberculosis. Neres J, Pojer F, Molteni E, Chiarelli LR, Dhar N, Boy-Röttger S, Buroni S, Fullam E, Degiacomi G, Lucarelli AP, Read RJ, Zanoni G, Edmondson DE, De Rossi E, Pasca MR, McKinney JD, Dyson PJ, Riccardi G, Mattevi A, Cole ST, Binda C. Sci Transl Med 4 150ra121 (2012)
  5. Structural characterization of glucooligosaccharide oxidase from Acremonium strictum. Lee MH, Lai WL, Lin SF, Hsu CS, Liaw SH, Tsai YC. Appl. Environ. Microbiol. 71 8881-8887 (2005)
  6. Molecular, phylogenetic and comparative genomic analysis of the cytokinin oxidase/dehydrogenase gene family in the Poaceae. Mameaux S, Cockram J, Thiel T, Steuernagel B, Stein N, Taudien S, Jack P, Werner P, Gray JC, Greenland AJ, Powell W. Plant Biotechnol. J. 10 67-82 (2012)
  7. Combinatorially selected defense peptides protect plant roots from pathogen infection. Fang ZD, Laskey JG, Huang S, Bilyeu KD, Morris RO, Schmidt FJ, English JT. Proc. Natl. Acad. Sci. U.S.A. 103 18444-18449 (2006)
  8. Crystal structure analysis of free and substrate-bound 6-hydroxy-L-nicotine oxidase from Arthrobacter nicotinovorans. Kachalova GS, Bourenkov GP, Mengesdorf T, Schenk S, Maun HR, Burghammer M, Riekel C, Decker K, Bartunik HD. J. Mol. Biol. 396 785-799 (2010)
  9. High-level expression and characterization of Zea mays cytokinin oxidase/dehydrogenase in Yarrowia lipolytica. Kopecný D, Pethe C, Sebela M, Houba-Hérin N, Madzak C, Majira A, Laloue M. Biochimie 87 1011-1022 (2005)
  10. Crystal structure of Arabidopsis thaliana cytokinin dehydrogenase. Bae E, Bingman CA, Bitto E, Aceti DJ, Phillips GN Jr. Proteins 70 303-306 (2008)
  11. Phenyl- and benzylurea cytokinins as competitive inhibitors of cytokinin oxidase/dehydrogenase: a structural study. Kopecný D, Briozzo P, Popelková H, Sebela M, Koncitíková R, Spíchal L, Nisler J, Madzak C, Frébort I, Laloue M, Houba-Hérin N. Biochimie 92 1052-1062 (2010)
  12. Brassinin oxidase mediated transformation of the phytoalexin brassinin: structure of the elusive co-product, deuterium isotope effect and stereoselectivity. Pedras MS, Minic Z, Sarma-Mamillapalle VK. Bioorg. Med. Chem. 19 1390-1399 (2011)
  13. Crystallization and preliminary X-ray diffraction analysis of the flax cytokinin oxidase LuCKX1.1. Wan L, Williams SJ, Zhang X, Ericsson DJ, Koeck M, Dodds PN, Ellis JG, Kobe B. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69 1094-1096 (2013)
  14. Implementation of pseudoreceptor-based pharmacophore queries in the prediction of probable protein targets: explorations in the protein structural profile of Zea mays. Kumar SP, Jha PC, Pandya HA, Jasrai YT. Mol Biosyst 10 1833-1844 (2014)