The TriTryp phosphatome: analysis of the protein phosphatase catalytic domains.
The TriTryp phosphatome: analysis of the protein phosphatase catalytic domains.
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DOI：
10.1186/1471-2164-8-434
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发表时间：
2007-11-26
期刊：
影响因子：
4.4
通讯作者：
Tabernero L
中科院分区：
文献类型：
--
作者：
Brenchley R;Tariq H;McElhinney H;Szöor B;Huxley-Jones J;Stevens R;Matthews K;Tabernero L
本文主要研究克氏锥虫、布氏锥虫和硕大利什曼原虫的基因组。这些寄生虫是造成破坏性人类疾病的罪魁祸首，这些疾病分别被称为恰加斯病、非洲昏睡病和皮肤利什曼病，影响到发展中世界的数百万人。这些被忽视的疾病的流行是贫穷、预防不足和难以治疗的综合结果。蛋白质磷酸化是控制这些动质体发育的重要机制。为了进一步了解这些生物的生物学，我们提出了三种寄生虫的磷酸酶补体（磷酸酶体）的表征。基于本体的扫描三个基因组被用来确定86磷酸酶催化结构域在T。cruzi，T. brucei和L.少校我们发现有趣的差异与其他真核生物的基因组，如酪氨酸磷酸酶的比例低和扩展的丝氨酸/苏氨酸磷酸酶家族。此外，在这些物种中鉴定出大量非典型蛋白磷酸酶，占总磷酸酶补体的三分之一以上。大多数非典型磷酸酶属于双特异性磷酸酶（DSP）家族，并且在结构域组织和序列特征方面与经典DSP表现出相当大的差异。磷酸酶体的三个动质体的分析表明，他们拥有直系同源的许多磷酸酶在其他真核生物，包括人类。然而，新的结构域架构和不寻常的组合的附件域，建议不同的功能作用的动质体磷酸酶，这有待进一步的实验探索。这些独特的性状可以利用蛋白磷酸酶抑制剂已经广泛的知识，在药物开发中选择合适的新靶点，以防止疾病的传播和扩散。
The genomes of the three parasitic protozoa Trypanosoma cruzi, Trypanosoma brucei and Leishmania major are the main subject of this study. These parasites are responsible for devastating human diseases known as Chagas disease, African sleeping sickness and cutaneous Leishmaniasis, respectively, that affect millions of people in the developing world. The prevalence of these neglected diseases results from a combination of poverty, inadequate prevention and difficult treatment. Protein phosphorylation is an important mechanism of controlling the development of these kinetoplastids. With the aim to further our knowledge of the biology of these organisms we present a characterisation of the phosphatase complement (phosphatome) of the three parasites. An ontology-based scan of the three genomes was used to identify 86 phosphatase catalytic domains in T. cruzi, 78 in T. brucei, and 88 in L. major. We found interesting differences with other eukaryotic genomes, such as the low proportion of tyrosine phosphatases and the expansion of the serine/threonine phosphatase family. Additionally, a large number of atypical protein phosphatases were identified in these species, representing more than one third of the total phosphatase complement. Most of the atypical phosphatases belong to the dual-specificity phosphatase (DSP) family and show considerable divergence from classic DSPs in both the domain organisation and sequence features. The analysis of the phosphatome of the three kinetoplastids indicates that they possess orthologues to many of the phosphatases reported in other eukaryotes, including humans. However, novel domain architectures and unusual combinations of accessory domains, suggest distinct functional roles for several of the kinetoplastid phosphatases, which await further experimental exploration. These distinct traits may be exploited in the selection of suitable new targets for drug development to prevent transmission and spread of the diseases, taking advantage of the already extensive knowledge on protein phosphatase inhibitors.
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影响因子：
16
作者：
Begley, MJ;Taylor, GS;Stuckey, JA
通讯作者：
Stuckey, JA
DOI：
10.1002/prot.340170405
发表时间：
1993-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
BORK, P
通讯作者：
BORK, P
影响因子：
3.4
作者：
Black, DS;Marie-Cardine, A;Bliska, JB
通讯作者：
Bliska, JB
DOI：
10.1073/pnas.241397198
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, MS;Guan, Z;Su, XD
通讯作者：
Su, XD
影响因子：
8
作者：
Bork, P;Brown, NP;Schultz, J
通讯作者：
Schultz, J