Nucleotide binding by the histidine kinase CheA

Bilwes AM.; Croal LR.; Crane BR.; Simon MI.; Quezada CM.

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Nucleotide binding by the histidine kinase CheA

机译：组氨酸激酶CheA结合核苷酸

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To probe the structural basis for protein histidine kinase (PHK) catalytic activity and the prospects for PHK-specific inhibitor design, we report the crystal structures for the nucleotide binding domain of Thermotoga maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP) bound with either Mg2+ or Mn2+. The conformation of ADPNP bound to CheA and related ATPases differs from that reported in the ADPNP complex of PHK EnvZ. Interactions of the active site with the nucleotide gamma -phosphate and its associated Mg2+ ion are linked to conformational changes in an ATP-lid that could mediate recognition of the substrate domain. The inhibitor TNP-ATP binds CheA with its phosphates in a nonproductive conformation and its adenine and trinitrophenyl groups in two adjacent binding pockets. The trinitrophenyl interaction may be exploited for designing CheA-targeted drugs that would not interfere with host ATPases. [References: 44]

机译：为了探索蛋白质组氨酸激酶（PHK）催化活性的结构基础以及PHK特异性抑制剂设计的前景，我们报告了嗜热栖热菌CheA与ADP和三种ATP类似物（ADPNP，ADPCP和TNP）的核苷酸结合结构域的晶体结构-ATP）与Mg2 +或Mn2 +结合。与CheA和相关ATP酶结合的ADPNP构象与PHK EnvZ的ADPNP复合物中报道的构象不同。活性位点与核苷酸γ-磷酸及其相关的Mg2 +离子的相互作用与ATP盖中的构象变化有关，该构象变化可介导对底物结构域的识别。抑制剂TNP-ATP以非生产性构型将CheA与它的磷酸盐结合，并在两个相邻的结合袋中结合其腺嘌呤和三硝基苯基。可以利用三硝基苯基相互作用来设计不会干扰宿主ATPase的CheA靶向药物。 [参考：44]

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《Nature structural biology》 |2001年第4期|共8页
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Bilwes AM.; Croal LR.; Crane BR.; Simon MI.; Quezada CM.;
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1. Nucleotide binding by the histidine kinase CheA [J] . Bilwes AM., Croal LR., Crane BR., Nature structural biology . 2001,第4期

机译：组氨酸激酶CheA结合核苷酸
2. Structure of the CheY-binding domain of histidine kinase CheA in complex with CheY [J] . Welch M., Mourey L., Birck C., Nature structural biology . 1998,第1期

机译：组氨酸激酶CheA的CheY结合结构域与CheY复合
3. Probing the nucleotide binding and phosphorylation by the histidine kinase of a novel three-protein two-component system from Mycobacterium tuberculosis [J] . Rashmi Shrivastava, Ananta Kumar Ghosh, Amit Kumar Das FEBS letters. . 2007,第9期

机译：结核分枝杆菌新型三蛋白两组分系统的组氨酸激酶探测核苷酸结合和磷酸化
4. Metal Ion Binding in Deprotonated Histidine Peptides - Solution pH Can Affect Electrosprayed Metal-Ion Binding Patterns [C] . Robert C. Dunbar, Jonathan Martens, Giel Berden, ASMS Conference on Mass Spectrometry and Allied Topics . 2016

机译：在去质子化的组氨酸肽中的金属离子结合 - 溶液pH可以影响电喷雾金属离子结合图案
5. NMR studies of the domain fragments CheA(1-134) and CheA(1-233) of the histidine autokinase CheA from Escherichia coli and resonance assignments of the receptor coupling protein CheW from Thermotoga maritima. [D] . Zhou, Hongjun. 1996

机译：来自大肠杆菌的组氨酸自身激酶CheA的结构域片段CheA（1-134）和CheA（1-233）的NMR研究以及来自滨海嗜热菌的受体偶联蛋白CheW的共振分配。
6. The receiver domain of FrzE a CheA-CheY fusion protein regulates the CheA histidine kinase activity and downstream signaling to the A- and S-motility systems of Myxococcus xanthus [O] . Yuki F. Inclán, Sophie Laurent, David R. Zusman -1

机译：Cher-CheY融合蛋白FrzE的受体结构域可调节CheA组氨酸激酶的活性和向X粘球菌A-和S-运动系统的下游信号传导
7. Probing the nucleotide binding and phosphorylation by the histidine kinase of a novel three-protein two-component system from Mycobacterium tuberculosis [O] . Shrivastava Rashmi, Ghosh Ananta Kumar, Das Amit Kumar 2007

机译：探索结核分枝杆菌新型三蛋白两组分系统的组氨酸激酶的核苷酸结合和磷酸化

Nucleotide binding by the histidine kinase CheA

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