Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB.
Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB.
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DOI：
10.1126/science.1163806
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发表时间：
2009-01-16
期刊：
影响因子：
--
通讯作者：
Brennan RG
中科院分区：
文献类型：
--
作者：
Schumacher MA;Piro KM;Xu W;Hansen S;Lewis K;Brennan RG
细菌对多种药物的耐受性在很大程度上是抗生素无法根除感染的原因，它是由一小群被称为持久性细菌的休眠细菌引起的。HipA是一种关键的大肠杆菌持久性因子，通常被转录抑制因子hib中和，hib也调节hipBA的表达。在这里，我们报道了HipA的多种结构和HipA- hib - dna复合物。HipA具有真核丝氨酸/苏氨酸激酶样折叠，可使翻译因子EF-Tu磷酸化，表明其通过细胞停滞存在。HipA-HipB-DNA结构揭示了hipb -操作符结合机制、~70°DNA弯曲和意想不到的HipA-DNA接触。二聚体hib与两个HipA分子相互作用，通过隔离和构象失活抑制其激酶活性。综上所述，这些研究提示了hipa介导的持久性及其被hib中和的机制。
Bacterial multidrug tolerance is largely responsible for the inability of antibiotics to eradicate infections and is caused by a small population of dormant bacteria called persisters. HipA is a critical Escherichia coli persistence factor that is normally neutralized by HipB, a transcription repressor, which also regulates hipBA expression. Here we report multiple structures of HipA and a HipA-HipB-DNA complex. HipA has a eukaryotic Ser/Thr kinase-like fold and can phosphorylate the translation factor, EF-Tu, suggesting a persistence mechanism via cell stasis. The HipA-HipB-DNA structure reveals the HipB-operator binding mechanism, ~70° DNA bending and unexpected HipA-DNA contacts. Dimeric HipB interacts with two HipA molecules to inhibit its kinase activity through sequestration and conformational inactivation. Combined, these studies suggest mechanisms for HipA-mediated persistence and its neutralization by HipB.
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影响因子：
3.2
作者：
MOYED, HS;BRODERICK, SH
通讯作者：
BRODERICK, SH
影响因子：
11.4
作者：
Honda, R;Lowe, ED;Johnson, LN
通讯作者：
Johnson, LN
影响因子：
3.2
作者：
BLACK, DS;KELLY, AJ;MOYED, HS
通讯作者：
MOYED, HS
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
14.9
作者：
Papapanagiotou, I.;Streeter, S. D.;Kneale, G. G.
通讯作者：
Kneale, G. G.