Nucleotide binding by the histidine kinase CheA

被引：139

作者：

Bilwes, AM ^{[1
]}

Quezada, CM ^{[1
]}

Croal, LR ^{[1
]}

Crane, BR ^{[1
]}

Simon, MI ^{[1
]}

机构：

[1] CALTECH, Div Biol, Pasadena, CA 91125 USA

来源：

NATURE STRUCTURAL BIOLOGY | 2001年 / 8卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/86243

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：353 / 360

页数：8

共 44 条

[1] Crystal structure and ATPase activity of MutL: Implications for DNA repair and mutagenesis [J].