Complexes of bacterial nicotinate mononucleotide adenylyltransferase with inhibitors: implication for structure-based drug design and improvement.
Complexes of bacterial nicotinate mononucleotide adenylyltransferase with inhibitors: implication for structure-based drug design and improvement.
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DOI：
10.1021/jm100377f
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发表时间：
2010-07-22
影响因子：
7.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Huang N;Kolhatkar R;Eyobo Y;Sorci L;Rodionova I;Osterman AL;Mackerell AD;Zhang H
由必需基因nadD编码的细菌烟酸单核苷酸腺苷酰转移酶在氧化还原辅因子NAD+的合成中起核心作用。NadD酶在大多数细菌物种中是保守的，并且已被认为是开发新的和潜在的广谱抗菌治疗剂的新靶标。在这里，我们报告的晶体结构的炭疽芽孢杆菌NadD与三个NadD抑制剂，包括本研究中合成的两个类似物的复合物。这些结构揭示了不同类别的NadD抑制剂共享的共同结合位点，并探索了该位点周围的化学环境。这里获得的结构数据还表明，配体结构的细微变化可以导致结合模式的显着变化，这些信息将有助于未来基于结构的优化和高亲和力抑制剂的设计。
Bacterial nicotinate mononucleotide adenylyltransferase encoded by the essential gene nadD plays a central role in the synthesis of the redox cofactor NAD+. The NadD enzyme is conserved in the majority of bacterial species and has been recognized as a novel target for developing new and potentially broad-spectrum antibacterial therapeutics. Here we report the crystal structures of Bacillus anthracis NadD in complex with three NadD inhibitors, including two analogues synthesized in the present study. These structures revealed a common binding site shared by different classes of NadD inhibitors and explored the chemical environment surrounding this site. The structural data obtained here also showed that the subtle changes in ligand structure can lead to significant changes in the binding mode, information that will be useful for future structure-based optimization and design of high affinity inhibitors.
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影响因子：
2.9
作者：
Cogan, EB;Birrell, GB;Griffith, OH
通讯作者：
Griffith, OH
DOI：
10.1126/science.1176667
发表时间：
2009-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fischbach MA;Walsh CT
通讯作者：
Walsh CT
影响因子：
3.7
作者：
Falagas ME;Bliziotis IA;Kasiakou SK;Samonis G;Athanassopoulou P;Michalopoulos A
通讯作者：
Michalopoulos A
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC