Poster Presentation The 46th Lorne Conference on Protein Structure and Function 2021

New Intermediates and New Reactions of Cysteine Dioxygenase (#222)

Zahra Shirani-Sarmazeh 1 , Jesse Gordon 2 , Christos Pierides 3 , David P Goldberg 2 , Samuel P deVisser 3 , Sigurd Wilbanks 4 , Guy N L Jameson 1
  1. The University of Melbourne, Parkville, Victoria, Australia
  2. Department of Chemistry, Johns Hopkins University, Baltimore, Maryland, USA
  3. Department of Chemical Engineering & Analytical Science, The University of Manchester, Manchester, United Kingdom
  4. Biochemistry, The University of Otago, Dunedin, New Zealand

Cysteine dioxygenase is a small 23kDa cupin-fold protein that catalyses the oxidation of cysteine to cysteine sulfinate through the addition of molecular oxygen. It catalyses the first and rate-determining step in the breakdown of cysteine into taurine and sulphate. The catalytic cycle occurs at a ferrous iron atom coordinated via three histidine residues. Crystal structures, spectroscopic studies and model complexes show cysteine binding via the thiol and amine to leave the sixth coordination site, the dioxygen binding site, partially occupied by a water molecule.1 Reactions under single turnover conditions have revealed an initial intermediate2 that is possibly an iron-superoxo.3 Similar initial intermediates are formed in the catalytic cycle of IPNS4 during penicillin biosynthesis but in this case the superoxo species carries out hydrogen atom abstraction rather than sulfur oxygenation. We are using a combined protein and small molecule model approach, in partnership with DFT to understand the mechanism of cysteine dioxygenase and understand how reactivity is controlled. We will describe in this presentation evidence we have for this and further intermediates along the reaction pathway.

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  2. E.P. Tchesnokov, A.S. Faponle, C.G. Davies, M.G. Quesne, R. Turner, M. Fellner, R.J. Souness, S.M. Wilbanks, S.P. de Visser, G.N.L. Jameson Chem. Commun. 2016, 52, 8814
  3. M.N. Blakely, M.A. Dedushko, P.C.Y. Poon, G. Villar-Acevedo, J. Kovacs J. Am. Chem. Soc. 2019, 141, 1867
  4. E.Y. Tamanaha, B. Zhang, Y. Guo, W-C. Chang, E.W. Barr, G. Xing, J. St Clair, S. Ye, F. Neese, J.M. Bollinger Jr., C. Krebs, J. Am. Chem. Soc. 2016, 138, 8862