Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization
文献类型：期刊论文
| 作者 | Kong, Yun-hua; Zhang, Liang; Yang, Zheng-yi; Han, Cong; Hu, Li-hong; Jiang, Hua-liang ; Shen, Xu
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2008-07 |
| 卷号 | 29期号:7页码:870-876 |
| 关键词 | cystathionine gamma-synthase malonyl-CoA : acyl carrier protein transacylase beta-hydroxyacyl-ACP dehydratase inhibitor type complex structure |
| ISSN号 | 1671-4083 |
| DOI | 10.1111/j.1745-7254.2008.00808.x |
| 文献子类 | Article |
| 英文摘要 | Aim: To investigate the inhibition features of the natural product juglone (5-hydroxy-1,4-naphthoquinone) against the three key enzymes from Helicobacter pylori (cystathionine gamma-synthase [HpCGS], malonyl-CoA:acyl carrier protein transacylase [HpFabD], and beta-hydroxyacyl-ACP dehydratase [HpFabZ]). Methods: An enzyme inhibition assay against HpCGS was carried out by using a continuous coupled spectrophotometric assay approach. The inhibition assay of HpFabD was performed based on the alpha-ketoglutarate dehydrogenase-coupled system, while the inhibition assay for HpFabZ was monitored by detecting the decrease in absorbance at 260 nm with crotonoyl-CoA conversion to beta-hydroxybutyryl-CoA. The juglone/FabZ complex crystal was obtained by soaking juglone into the HpFabZ crystal, and the X-ray crystal structure of the complex was analyzed by molecular replacement approach. Results: Juglone was shown to potently inhibit HpCGS, HpFabD, and HpFabZ with the half maximal inhibitory concentration IC50 values of 7.0 +/- 0.7, 20 +/- 1, and 30 +/- 4 mu mol/L, respectively. An inhibition-type study indicated that juglone was a non-competitive inhibitor of HpCGS against O-succinyl-L-homoserine (K-i=alpha K-i=24 mu mol/L), an uncompetitive inhibitor of HpFabD against malonyl-CoA (alpha K-i=7.4 mu mol/L), and a competitive inhibitor of HpFabZ against crotonoyl-CoA (K-i=6.8 mu mol/L). Moreover, the crystal structure of the HpFabZ/juglone complex further revealed the essential binding pattern of juglone against HpFabZ at the atomic level. Conclusion: HpCGS, HpFabD, and HpFabZ are potential targets of juglone. |
| WOS关键词 | FATTY-ACID BIOSYNTHESIS ; CYSTATHIONINE GAMMA-SYNTHASE ; CARRIER PROTEIN TRANSACYLASE ; ESCHERICHIA-COLI ; PLASMODIUM-FALCIPARUM ; DEHYDRATASE FABZ ; ENZYMATIC CHARACTERIZATION ; GENERAL-PROPERTIES ; COENZYME ; DISCOVERY |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3301336 |
| WOS记录号 | WOS:000257701000013 |
| 出版者 | BLACKWELL PUBLISHING |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272869]  |
| 专题 | 上海中药现代化研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第三研究室 |
| 通讯作者 | Hu, Li-hong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Kong, Yun-hua,Zhang, Liang,Yang, Zheng-yi,et al. Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization[J]. ACTA PHARMACOLOGICA SINICA,2008,29(7):870-876. |
| APA | Kong, Yun-hua.,Zhang, Liang.,Yang, Zheng-yi.,Han, Cong.,Hu, Li-hong.,...&Shen, Xu.(2008).Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization.ACTA PHARMACOLOGICA SINICA,29(7),870-876. |
| MLA | Kong, Yun-hua,et al."Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization".ACTA PHARMACOLOGICA SINICA 29.7(2008):870-876. |
入库方式： OAI收割
来源：上海药物研究所
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