The specific, submicromolar-Km ADP-ribose pyrophosphatase purified from human placenta is enzymically indistinguishable from recombinant NUDT9 protein, including a selectivity for Mn2+ as activating cation and increase in Km for ADP-ribose, both elicited by H2O2

被引:10
作者
Carloto, Antonio
Costas, Maria Jesus
Cameselle, Jose Carlos
McLennan, Alexander G.
Ribeiro, Joao Meireles [1 ]
机构
[1] Univ Extremadura, Fac Med, Unidad Bioquim & Biol Mol, E-06080 Badajoz, Spain
[2] Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2006年 / 1760卷 / 10期
基金
英国惠康基金;
关键词
adenosine diphosphate ribose; adenosine diphosphate ribose pyrophosphatase; hydrogen peroxide; nudix hydrolase; oxidative stress;
D O I
10.1016/j.bbagen.2006.06.003
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
Free ADP-ribose is a putative second messenger and also a potentially toxic compound due to its non-enzymic reactivity towards protein side chains. ADP-ribose hydrolysis is catalysed by NDP-sugar/alcohol pyrophosphatases of differing specificity, including a highly specific, low-K-m. ADP-ribose pyrophosphatase. In humans, a submicromolar-K-m ADP-ribose pyrophosphatase has been purified from placenta, while recombinant NUDT9 has been described as a similarly specific enzyme with a nudix motif, but with a 10(2)-10(3) higher K-m. Here, a comparative study of both proteins is presented showing that they are in fact enzymically indistinguishable; crucially, they both have submicromolar K-m for ADP-ribose. This study firmly supports the view that the ADP-ribose pyrophosphatase present in human tissues is a product of the NUDT9 gene. In addition, this study reveals previously unknown properties of both enzyme forms. They display the same, differential properties in the presence of Mg2+ or Mn2+ as activating cations with respect to substrate specificity, ADP-ribose saturation kinetics, and inhibition by fluoride. Treatment with H2O2 alters the Mg2+/Mn2+ responses and increases the K-m, values for ADP-ribose, changes that are reversed by DTT. The results are discussed in relation to the proposed roles for ADP-ribose in oxidative/nitrosative stress and for ADP-ribose pyrophosphatase as a protective enzyme whose function is to limit the intracellular accumulation of ADP-ribose. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:1545 / 1551
页数:7
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