Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.

Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.
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肺炎链球菌的断裂 - 重新结构域IV:革兰氏阳性喹诺酮靶标的晶体结构。

DOI:
10.1371/journal.pone.0000301
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发表时间:
2007-03-21
期刊:
影响因子:
3.7
通讯作者:
Sanderson MR
Sanderson MR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Laponogov I;Veselkov DA;Sohi MK;Pan XS;Achari A;Yang C;Ferrara JD;Fisher LM;Sanderson MR

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来自肺炎链球菌的拓扑异构酶(topo)IV亚基A(ParC)的55 kDa N-末端断裂-团聚结构域的2.7 kDa晶体结构,是革兰氏阳性细菌中喹诺酮靶点的第一个晶体结构,已被解决,并揭示了一个与大肠杆菌DNA促旋酶亚基A(GyrA)折叠相似的“闭合”二聚体,但不同于大肠杆菌ParC的“开放”门结构。与GyrA的DNA结合沟大部分带正电荷不同,ParC的DNA结合位点表现出与DNA的沟和磷酸骨架的预测位置一致的交替的带正电荷和带负电荷的区域的独特模式。基于ParC结构,提出了一种新的基于ParC的序列特异性识别门(G)段的诱导拟合模型.这些功能可能占肺炎球菌II型拓扑异构酶的独特的DNA识别和喹诺酮靶向性能相比,他们的革兰氏阴性。
The 2.7 Å crystal structure of the 55-kDa N-terminal breakage-reunion domain of topoisomerase (topo) IV subunit A (ParC) from Streptococcus pneumoniae, the first for the quinolone targets from a gram-positive bacterium, has been solved and reveals a ‘closed’ dimer similar in fold to Escherichia coli DNA gyrase subunit A (GyrA), but distinct from the ‘open’ gate structure of Escherichia coli ParC. Unlike GyrA whose DNA binding groove is largely positively charged, the DNA binding site of ParC exhibits a distinct pattern of alternating positively and negatively charged regions coincident with the predicted positions of the grooves and phosphate backbone of DNA. Based on the ParC structure, a new induced-fit model for sequence-specific recognition of the gate (G) segment by ParC has been proposed. These features may account for the unique DNA recognition and quinolone targeting properties of pneumococcal type II topoisomerases compared to their gram-negative counterparts.
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