Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4.

Jeong DG; Yoon TS; Jung SKPark BCPark HRyu SEKim SJ

首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4.

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Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4.

机译：除了催化探索结合位点晶体结构的催化核心MKP-4领域。

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Map kinase phosphatase 4 (MKP-4), which has been implicated in signalling pathways that negatively regulate glucose uptake, belongs to the dual-specificity phosphatase (DUSP) family. An inherent property of MKPs is an ability to undergo structural rearrangement, transitioning from a partially active to a fully active conformation. Here, a 2.7 A resolution crystal structure of the catalytic domain of MKP-4 (MKP-4C) is presented. It was determined that the MKP-4C structure seriously deviates from canonical conformations of DUSPs and this characteristic feature results in significant gaps between the catalytic core and several surrounding loops which are unique compared with other MKP counterparts that adopt an active conformation. Using virtual library screening, it was found that inhibitors bind to MKP-4C with high affinity near these gaps. Inhibitors that target other binding sites instead of the active site can be utilized to prevent transition to a fully active conformation. Compounds that are able to make contacts with these sites in MKP-4 would not only provide a beneficial increase in affinity but may also permit greater specificity relative to other protein tyrosine phosphatases.

机译：Map激酶磷酸酶4 (MKP-4)与消极的信号通路调节葡萄糖吸收,属于dual-specificity磷酸酶(DUSP)的家庭。固有财产MKPs的能力进行结构重组,转变从部分活跃充分活跃构象。MKP-4催化结构域(MKP-4C)。MKP-4C结构严重背离规范DUSPs这的构象特征显著催化核心和几个之间的差距独特的与周围循环采用积极的其他MKP同行构象。发现抑制剂结合MKP-4C高亲和力接近这些漏洞。目标其他绑定网站而不是积极的防止过渡到一个网站可以利用充分活跃的构象。在MKP-4能够接触这些网站不仅会提供有益的增加亲和力,但也可能允许更大的特异性相对于其它蛋白质酪氨酸磷酸酶。

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《Acta crystallographica.Section D. Biological crystallography》 |2011年第1期|25-31|共7页
作者
Jeong DG; Yoon TS; Jung SKPark BCPark HRyu SEKim SJ;
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作者单位

Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-Gu, Daejeon, Republic of Korea.;

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正文语种英语
中图分类化学;
关键词
Catalytic Domain; DUSP9 gene; Protein Tyrosine Phosphatasescrystal structure;

机译：催化领域;DUSP9基因;蛋白质酪氨酸Phosphatasescrystal结构;

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Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4.

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