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Structural and biochemical studies of sulphotransferase 18 from Arabidopsis thaliana explain its substrate specificity and reaction mechanism

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Authors

  • Felix Hirschmann
  • Petra Baruch
  • Igor Chizhov
  • Jonathan Wolf Mueller
  • Jutta Papenbrock

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External Research Organisations

  • Hannover Medical School (MHH)
  • University of Birmingham
  • Birmingham Health Partners
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Original languageEnglish
Article number4160
JournalScientific reports
Volume7
Issue number1
Publication statusPublished - 1 Dec 2017

Abstract

Sulphotransferases are a diverse group of enzymes catalysing the transfer of a sulfuryl group from 3′-phosphoadenosine 5′-phosphosulphate (PAPS) to a broad range of secondary metabolites. They exist in all kingdoms of life. In Arabidopsis thaliana (L.) Heynh. twenty-two sulphotransferase (SOT) isoforms were identified. Three of those are involved in glucosinolate (Gl) biosynthesis, glycosylated sulphur-containing aldoximes containing chemically different side chains, whose break-down products are involved in stress response against herbivores, pathogens, and abiotic stress. To explain the differences in substrate specificity of desulpho (ds)-Gl SOTs and to understand the reaction mechanism of plant SOTs, we determined the first high-resolution crystal structure of the plant ds-Gl SOT AtSOT18 in complex with 3′-phosphoadenosine 5′-phosphate (PAP) alone and together with the Gl sinigrin. These new structural insights into the determination of substrate specificity were complemented by mutagenesis studies. The structure of AtSOT18 invigorates the similarity between plant and mammalian sulphotransferases, which illustrates the evolutionary conservation of this multifunctional enzyme family. We identified the essential residues for substrate binding and catalysis and demonstrated that the catalytic mechanism is conserved between human and plant enzymes. Our study indicates that the loop-gating mechanism is likely to be a source of the substrate specificity in plants.

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Cite this

Structural and biochemical studies of sulphotransferase 18 from Arabidopsis thaliana explain its substrate specificity and reaction mechanism. / Hirschmann, Felix; Baruch, Petra; Chizhov, Igor et al.
In: Scientific reports, Vol. 7, No. 1, 4160, 01.12.2017.

Research output: Contribution to journalArticleResearchpeer review

Hirschmann F, Baruch P, Chizhov I, Mueller JW, Manstein DJ, Papenbrock J et al. Structural and biochemical studies of sulphotransferase 18 from Arabidopsis thaliana explain its substrate specificity and reaction mechanism. Scientific reports. 2017 Dec 1;7(1):4160. doi: 10.1038/s41598-017-04539-2
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title = "Structural and biochemical studies of sulphotransferase 18 from Arabidopsis thaliana explain its substrate specificity and reaction mechanism",
abstract = "Sulphotransferases are a diverse group of enzymes catalysing the transfer of a sulfuryl group from 3′-phosphoadenosine 5′-phosphosulphate (PAPS) to a broad range of secondary metabolites. They exist in all kingdoms of life. In Arabidopsis thaliana (L.) Heynh. twenty-two sulphotransferase (SOT) isoforms were identified. Three of those are involved in glucosinolate (Gl) biosynthesis, glycosylated sulphur-containing aldoximes containing chemically different side chains, whose break-down products are involved in stress response against herbivores, pathogens, and abiotic stress. To explain the differences in substrate specificity of desulpho (ds)-Gl SOTs and to understand the reaction mechanism of plant SOTs, we determined the first high-resolution crystal structure of the plant ds-Gl SOT AtSOT18 in complex with 3′-phosphoadenosine 5′-phosphate (PAP) alone and together with the Gl sinigrin. These new structural insights into the determination of substrate specificity were complemented by mutagenesis studies. The structure of AtSOT18 invigorates the similarity between plant and mammalian sulphotransferases, which illustrates the evolutionary conservation of this multifunctional enzyme family. We identified the essential residues for substrate binding and catalysis and demonstrated that the catalytic mechanism is conserved between human and plant enzymes. Our study indicates that the loop-gating mechanism is likely to be a source of the substrate specificity in plants.",
author = "Felix Hirschmann and Petra Baruch and Igor Chizhov and Mueller, {Jonathan Wolf} and Manstein, {Dietmar J.} and Jutta Papenbrock and Roman Fedorov and Florian Krause",
note = "Funding information: We would like to thank Julia Volker, Leibniz University Hannover, for valuable technical assistance. Initial screening for crystallization conditions was done by Prof. Dr. George N. Phillips, Jr., University of Wisconsin-Madison, USA, within the Protein Structure Initiative. We gratefully thank the staff scientists at the synchrotron beamline ID23-1, ESRF/Grenoble, for their assistance during diffraction data collection. This work was partially financed by the German Research Foundation (PA 764/10-1). RF was supported by the German Research Foundation (FE 1510/2-1). JWM was funded by the European Commission (Marie Curie Fellowship 625451 SUPA-HD, Sulphation pathways in Health and Disease). The publication of this article was funded by the Open Access Fund of the Leibniz Universit{\"a}t Hannover.",
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AU - Hirschmann, Felix

AU - Baruch, Petra

AU - Chizhov, Igor

AU - Mueller, Jonathan Wolf

AU - Manstein, Dietmar J.

AU - Papenbrock, Jutta

AU - Fedorov, Roman

AU - Krause, Florian

N1 - Funding information: We would like to thank Julia Volker, Leibniz University Hannover, for valuable technical assistance. Initial screening for crystallization conditions was done by Prof. Dr. George N. Phillips, Jr., University of Wisconsin-Madison, USA, within the Protein Structure Initiative. We gratefully thank the staff scientists at the synchrotron beamline ID23-1, ESRF/Grenoble, for their assistance during diffraction data collection. This work was partially financed by the German Research Foundation (PA 764/10-1). RF was supported by the German Research Foundation (FE 1510/2-1). JWM was funded by the European Commission (Marie Curie Fellowship 625451 SUPA-HD, Sulphation pathways in Health and Disease). The publication of this article was funded by the Open Access Fund of the Leibniz Universität Hannover.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Sulphotransferases are a diverse group of enzymes catalysing the transfer of a sulfuryl group from 3′-phosphoadenosine 5′-phosphosulphate (PAPS) to a broad range of secondary metabolites. They exist in all kingdoms of life. In Arabidopsis thaliana (L.) Heynh. twenty-two sulphotransferase (SOT) isoforms were identified. Three of those are involved in glucosinolate (Gl) biosynthesis, glycosylated sulphur-containing aldoximes containing chemically different side chains, whose break-down products are involved in stress response against herbivores, pathogens, and abiotic stress. To explain the differences in substrate specificity of desulpho (ds)-Gl SOTs and to understand the reaction mechanism of plant SOTs, we determined the first high-resolution crystal structure of the plant ds-Gl SOT AtSOT18 in complex with 3′-phosphoadenosine 5′-phosphate (PAP) alone and together with the Gl sinigrin. These new structural insights into the determination of substrate specificity were complemented by mutagenesis studies. The structure of AtSOT18 invigorates the similarity between plant and mammalian sulphotransferases, which illustrates the evolutionary conservation of this multifunctional enzyme family. We identified the essential residues for substrate binding and catalysis and demonstrated that the catalytic mechanism is conserved between human and plant enzymes. Our study indicates that the loop-gating mechanism is likely to be a source of the substrate specificity in plants.

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