A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex

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A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex. / Grum, Daniel; van den Boom, Johannes; Neumann, Daniel; Matena, Anja; Link, Nina M; Mueller, Jonathan W.

In: Biochemical and Biophysical Research Communications, Vol. 395, No. 3, 07.05.2010, p. 420-5.

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Grum, Daniel ; van den Boom, Johannes ; Neumann, Daniel ; Matena, Anja ; Link, Nina M ; Mueller, Jonathan W. / A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 395, No. 3. pp. 420-5.

Bibtex

@article{7c82199e63c04a619fc2170761b02955,
title = "A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex",
abstract = "3'-Phospho-adenosine-5'-phosphosulphate (PAPS) synthases are fundamental to mammalian sulphate metabolism. These enzymes have recently been linked to a rising number of human diseases. Despite many studies, it is not yet understood how the mammalian PAPS synthases 1 and 2 interact with each other. We provide first evidence for heterodimerisation of these two enzymes by pull-down assays and F{\"o}rster resonance energy transfer (FRET) measurements. Kinetics of dimer dissociation/association indicates that these heterodimers form as soon as PAPSS1 and -S2 encounter each other in solution. Affinity of the homo- and heterodimers were found to be in the low nanomolar range using anisotropy measurements employing proteins labelled with the fluorescent dye IAEDANS that--in spite of its low quantum yield--is well suited for anisotropy due to its large Stokes shift. Within its kinase domain, the PAPS synthase heterodimer displays similar substrate inhibition by adenosine-5'-phosphosulphate (APS) as the homodimers. Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells.",
keywords = "Anisotropy, Enzyme Activation, Humans, Isoenzymes, Kinetics, Multienzyme Complexes, Protein Multimerization, Sulfate Adenylyltransferase, Sulfates",
author = "Daniel Grum and {van den Boom}, Johannes and Daniel Neumann and Anja Matena and Link, {Nina M} and Mueller, {Jonathan W}",
note = "Copyright (c) 2010 Elsevier Inc. All rights reserved.",
year = "2010",
month = may,
day = "7",
doi = "10.1016/j.bbrc.2010.04.039",
language = "English",
volume = "395",
pages = "420--5",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex

AU - Grum, Daniel

AU - van den Boom, Johannes

AU - Neumann, Daniel

AU - Matena, Anja

AU - Link, Nina M

AU - Mueller, Jonathan W

N1 - Copyright (c) 2010 Elsevier Inc. All rights reserved.

PY - 2010/5/7

Y1 - 2010/5/7

N2 - 3'-Phospho-adenosine-5'-phosphosulphate (PAPS) synthases are fundamental to mammalian sulphate metabolism. These enzymes have recently been linked to a rising number of human diseases. Despite many studies, it is not yet understood how the mammalian PAPS synthases 1 and 2 interact with each other. We provide first evidence for heterodimerisation of these two enzymes by pull-down assays and Förster resonance energy transfer (FRET) measurements. Kinetics of dimer dissociation/association indicates that these heterodimers form as soon as PAPSS1 and -S2 encounter each other in solution. Affinity of the homo- and heterodimers were found to be in the low nanomolar range using anisotropy measurements employing proteins labelled with the fluorescent dye IAEDANS that--in spite of its low quantum yield--is well suited for anisotropy due to its large Stokes shift. Within its kinase domain, the PAPS synthase heterodimer displays similar substrate inhibition by adenosine-5'-phosphosulphate (APS) as the homodimers. Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells.

AB - 3'-Phospho-adenosine-5'-phosphosulphate (PAPS) synthases are fundamental to mammalian sulphate metabolism. These enzymes have recently been linked to a rising number of human diseases. Despite many studies, it is not yet understood how the mammalian PAPS synthases 1 and 2 interact with each other. We provide first evidence for heterodimerisation of these two enzymes by pull-down assays and Förster resonance energy transfer (FRET) measurements. Kinetics of dimer dissociation/association indicates that these heterodimers form as soon as PAPSS1 and -S2 encounter each other in solution. Affinity of the homo- and heterodimers were found to be in the low nanomolar range using anisotropy measurements employing proteins labelled with the fluorescent dye IAEDANS that--in spite of its low quantum yield--is well suited for anisotropy due to its large Stokes shift. Within its kinase domain, the PAPS synthase heterodimer displays similar substrate inhibition by adenosine-5'-phosphosulphate (APS) as the homodimers. Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells.

KW - Anisotropy

KW - Enzyme Activation

KW - Humans

KW - Isoenzymes

KW - Kinetics

KW - Multienzyme Complexes

KW - Protein Multimerization

KW - Sulfate Adenylyltransferase

KW - Sulfates

U2 - 10.1016/j.bbrc.2010.04.039

DO - 10.1016/j.bbrc.2010.04.039

M3 - Article

C2 - 20382111

VL - 395

SP - 420

EP - 425

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -