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

被引:29
作者
Grum, Daniel [1 ]
van den Boom, Johannes [1 ]
Neumann, Daniel [1 ]
Matena, Anja [1 ]
Link, Nina M. [1 ]
Mueller, Jonathan W. [1 ]
机构
[1] Univ Duisburg Essen, Fac Biol & Geog, Ctr Med Biotechnol ZMB, D-45117 Essen, Germany
关键词
PAPS synthase; Heterodimer; Anisotropy; FRET; Fluorescence; Sulfate activation; KINETIC-PROPERTIES; CRYSTAL-STRUCTURE; ATP SULFURYLASE; KINASE DOMAIN; SYNTHETASE-1; EXPRESSION; LOCALIZATION; ENZYME; INHIBITION; MUTATIONS;
D O I
10.1016/j.bbrc.2010.04.039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Forster 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. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:420 / 425
页数:6
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