4-Hydroxyphenylpyruvate dioxygenase: a hybrid density functional study of the catalytic reaction mechanism

Biochemistry
Tomasz BorowskiPer E M Siegbahn

Abstract

Density functional calculations using the B3LYP functional has been used to study the reaction mechanism of 4-hydroxyphenylpyruvate dioxygenase. The first part of the catalytic reaction, dioxygen activation, is found to have the same mechanism as in alpha-ketoglutarate-dependent enzymes; the ternary enzyme-substrate-dioxygen complex is first decarboxylated to the iron(II)-peracid intermediate, followed by heterolytic cleavage of the O-O bond yielding an iron(IV)-oxo species. This highly reactive intermediate attacks the aromatic ring at the C1 position and forms a radical sigma complex, which can either form an arene oxide or undergo a C1-C2 side-chain migration. The arene oxide is found to have no catalytic relevance. The side-chain migration is a two-step process; the carbon-carbon bond cleavage first affords a biradical intermediate, followed by a decay of this species forming the new C-C bond. The ketone intermediate formed by a 1,2 shift of an acetic acid group rearomatizes either at the active site of the enzyme or in solution. The hypothetical oxidation of the aromatic ring at the C2 position was also studied to shed light on the 4-HPPD product specificity. In addition, the benzylic hydroxylation reaction, catalyzed by 4...Continue Reading

References

Dec 16, 1970·Journal of the American Chemical Society·B LindbladS Lindstedt
Jul 1, 1981·European Journal of Biochemistry·R LeinbergerJ Rétey
Nov 7, 1996·Chemical Reviews·Masanori SonoJohn H. Dawson
Jun 12, 2003·Journal of the American Chemical Society·Sam P de Visser, Sason Shaik
Jan 30, 2004·Journal of the American Chemical Society·Denis A ProshlyakovRobert P Hausinger
Feb 24, 2004·Chemistry : a European Journal·Tomasz BorowskiPer E M Siegbahn

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Citations

Oct 29, 2005·Drug Discovery Today·Adrian J Mulholland
Dec 7, 2007·Journal of the American Chemical Society·Andrea DeckerEdward I Solomon
Aug 27, 2010·Journal of the American Chemical Society·Tomasz BorowskiPer E M Siegbahn
Mar 24, 2010·Chemical Communications : Chem Comm·Richard LonsdaleAdrian J Mulholland
Mar 13, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Andrew J FieldingLawrence Que
Aug 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michael L NeidigEdward I Solomon
Nov 19, 2014·Journal of Agricultural and Food Chemistry·Da-Wei WangGuang-Fu Yang
Jun 23, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Valentin GeorgievPer E M Siegbahn
Apr 14, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Vincent Purpero, Graham R Moran
Dec 24, 2015·Chemistry : a European Journal·Matthew G QuesneSam P de Visser
Feb 10, 2016·The Journal of Physical Chemistry. a·Anna WójcikTomasz Borowski
Nov 26, 2008·Bioorganic & Medicinal Chemistry·Matthias Witschel
Mar 8, 2006·Journal of Computational Chemistry·Tomasz BorowskiPer E M Siegbahn
Nov 15, 2012·Chemistry : a European Journal·Anna MiłaczewskaTomasz Borowski
Mar 26, 2016·Current Opinion in Chemical Biology·Mark D White, Emily Flashman
Mar 4, 2006·Journal of Inorganic Biochemistry·Arianna BassanPer E M Siegbahn
Nov 22, 2013·Chemical Communications : Chem Comm·Sam P de VisserUlf Ryde
Nov 27, 2014·Frontiers in Chemistry·Hans M Senn
May 28, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Tibor András RokobLubomír Rulíšek
Jul 2, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Nathalie Proos Vedin, Marcus Lundberg
Oct 27, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Spencer C Peck, Wilfred A van der Donk
Mar 10, 2017·Inorganic Chemistry·Wen-Jie WeiRong-Zhen Liao
Jun 10, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ying FuFei Ye
Jul 11, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Per E M Siegbahn
Nov 14, 2019·Journal of Biochemistry·An-Ning FengHwei-Jen Lee
Mar 7, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Reza LatifiLaleh Tahsini
Sep 25, 2017·Pest Management Science·Hua-Bin LiYou-Quan Zhu
Apr 30, 2019·Frontiers in Chemistry·Matthew G QuesneC Richard A Catlow
Mar 18, 2020·Beilstein Journal of Organic Chemistry·Man-Man WangDa-Yong Zhang
Jul 1, 2005·Journal of Chemical Theory and Computation·Tomasz BorowskiPer E M Siegbahn
Apr 3, 2009·The Journal of Physical Chemistry. B·Haining LiuJames W Gauld
Oct 18, 2006·Accounts of Chemical Research·Per E M Siegbahn, Tomasz Borowski

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