Computational prediction of furin cleavage sites by a hybrid method and understanding mechanism underlying diseases.

Computational prediction of furin cleavage sites by a hybrid method and understanding mechanism underlying diseases.
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通过混合方法计算预测弗林蛋白酶切割位点并了解疾病的潜在机制

DOI:
10.1038/srep00261
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发表时间:
2012
期刊:
影响因子:
4.6
通讯作者:
Wu, Jianhua
Wu, Jianhua
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tian, Sun;Wang Huajun;Wu, Jianhua

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弗林蛋白酶在分泌途径中切割多种类型的蛋白质前体。弗林蛋白酶切割的底物具有特定的20个残基识别序列基序。在这份报告中,基于20个残基的序列基序的功能特性,我们开发了一个弗林蛋白酶切割位点预测工具,Pituitary,使用的混合方法组成的隐马尔可夫模型和生物知识为基础的累积概率得分函数。PIPE可以准确预测蛋白质序列中弗林蛋白酶切割位点的存在和位置,具有高灵敏度(96.9%)和高特异性(97.3%)。pipeline的预测分数是生物学上有意义的,并反映结合强度和溶剂的弗林蛋白酶底物的可及性。预测结果在细胞背景下进行解释:亚细胞定位,细胞功能和其他动态蛋白质修饰的干扰。结合下一代测序技术,Pierrin可以帮助阐明弗林蛋白酶切割相关人类疾病的分子机制。该文件已在相关网站上免费提供。
Furin cleaves diverse types of protein precursors in the secretory pathway. The substrates for furin cleavage possess a specific 20-residue recognition sequence motif. In this report, based on the functional characterisation of the 20-residue sequence motif, we developed a furin cleavage site prediction tool, PiTou, using a hybrid method composed of a hidden Markov model and biological knowledge-based cumulative probability score functions. PiTou can accurately predict the presence and location of furin cleavage sites in protein sequences with high sensitivity (96.9%) and high specificity (97.3%). PiTou's prediction scores are biological meaningful and reflect binding strength and solvent accessibility of furin substrates. A prediction result is interpreted within cellular contexts: subcellular localisation, cellular function and interference by other dynamic protein modifications. Combining next-generation sequencing, PiTou can help with elucidating the molecular mechanism of furin cleavage-associated human diseases. PiTou has been made freely available at the associated website.
FurinDB:20 残基弗林蛋白酶切割位点基序、底物及其相关药物的数据库
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