Romá-Mateo Carlos, Ríos Pablo, Tabernero Lydia, Attwood Teresa K, Pulido Rafael
Centro de Investigación Príncipe Felipe, Avenida Autopista del Saler, 16-3, 46013 Valencia, Spain.
J Mol Biol. 2007 Dec 7;374(4):899-909. doi: 10.1016/j.jmb.2007.10.008. Epub 2007 Oct 11.
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.
蛋白质酪氨酸磷酸酶（PTPs）超家族的成员都具有一个进化上保守的PTP催化结构域。其中，双特异性磷酸酶（DSPs）在底物特异性方面构成了一组多样化的酶，包括非蛋白质底物。近年来，在多种生物体中发现了越来越多新型的DSPs，其功能和生物学底物尚未明确界定。在本研究中，我们定义了来自不同门的进化相关非典型DSPs的结构和功能特性。确定了一组保守基序，这些基序（i）将哺乳动物非典型DSPs与密切相关的酶独特地分开，并且（ii）专门表征了存在于植物、真菌和动基体中的一个新型非典型DSPs家族[植物和真菌非典型（PFA）-DSPs]；尽管具有不同的序列“指纹”，但PFA-DSPs的PTP三级结构是保守的。对PFA-DSPs催化特性的分析表明这些酶存在独特的底物特异性。我们的研究结果预测了PTPs的DSP家族不同成员的特征性功能基序，并为功能未知的DSPs的功能特性提供了见解。
