A novel phosphatase family, structurally related to dual-specificity phosphatases, that displays unique amino acid sequence and substrate specificity

A novel phosphatase family, structurally related to dual-specificity phosphatases, that displays unique amino acid sequence and substrate specificity
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DOI:
10.1016/j.jmb.2007.10.008
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发表时间:
2007-12-07
影响因子:
5.6
通讯作者:
Pulido, Rafael
Pulido, Rafael
中科院分区:
生物学2区
文献类型:
--
作者:
Roma-Mateo, Carlos;Rios, Pablo;Pulido, Rafael

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蛋白质酪氨酸磷酸酶(PTPS)的超家族成员共享进化保守的PTP催化结构域的存在。其中,双特异性磷酸酶(DSP)在包括非蛋白质底物在内的底物特异性方面构成了多种酶。近年来,在各种生物中都发现了越来越多的新型DSP,其功能和生物底物的定义不当。在这项研究中,我们定义了来自不同门的进化相关的非典型DSP的结构和功能特性。定义了一组保守的基序,即(i)与密切相关的酶的独特隔离哺乳动物非典型DSP,(ii)独家表征了一种新型的植物,真菌和动型植物中存在的非典型DSP家族[植物和真菌(PFA)-dsypical(pfa)-dsps -dsps -dsps- ;尽管具有不同的序列“指纹”,但PFA-DSPS的PTP三级结构仍然保存。对PFA-DSP的催化特性的分析表明,这些酶存在独特的底物特异性。我们的发现预测了PTP的DSP家族的不同成员的特征功能基序,并提供了对未知功能DSP的功能特性的见解。 (c)2007 Elsevier Ltd.保留所有权利。
Members of the superfamily of protein tyrosine phosphatases (PTPs) share the presence of an evolutionarily conserved PTP catalytic domain. Among them, the dual-specificity phosphatases (DSPs) constitute a diverse group of enzymes in terms of substrate specificity, including nonprotein substrates. In recent years, an increasing number of novel DSPs, whose functions and biological substrates are not well defined, have been discovered in a variety of organisms. In this study, we define the structural and functional properties of evolutionarily related atypical DSPs from different phyla. Sets of conserved motifs were defined that (i) uniquely segregated mammalian atypical DSPs from closely related enzymes and (ii) exclusively characterised a novel family of atypical DSPs present in plants, fungi, and kinetoplastids [plant and fungi atypical (PFA)-DSPs]; despite having different sequence "fingerprints," the PTP tertiary structure of PFA-DSPs is conserved. Analysis of the catalytic properties of PFA-DSPs suggests the existence of a unique substrate specificity for these enzymes. Our findings predict characteristic functional motifs for the diverse members of the DSP families of PTPs and provide insights into the functional properties of DSPs of unknown function. (C) 2007 Elsevier Ltd. All rights reserved.