Modulating the Substrate Specificity of LTA4H Aminopeptidase by Using Chemical Compounds and Small-Molecule-Guided Mutagenesis
文献类型：期刊论文
| 作者 | Jiang, Xiaolu1; Zhou, Lu1; Wu, Yiran1,2; Wei, Dengguo1,2; Sun, Chunyi1; Jia, Jia1; Liu, Ying1; Lai, Luhua1,2 |
| 刊名 | CHEMBIOCHEM
 |
| 出版日期 | 2010-05-17 |
| 卷号 | 11期号:8页码:1120-1128 |
| 关键词 | Aminopeptidase Activity Hydrolases Protein Engineering Selectivity Small Molecules |
| ISSN号 | 1439-4227 |
| DOI | 10.1002/cbic.200900788 |
| 英文摘要 | Leukotriene A(4) hydrolase (LTA4H) is a bifunctional zinc-containing enzyme with an epoxide hydrolase activity and an aminopeptidase activity of unclear function. The two activities occupy different, but overlapping sites. In this study we have focused on the non-overlapping regions of these sites and have found that a series of previously reported compounds-diphenyl ether, 4-phenoxyphenol, and their derivatives-can change the substrate specificity of LTA4H aminopeptidase, from arginyl peptide to alanyl peptide. The possible substrate specificity alteration mechanism was studied with the aid of molecular modeling and site-directed mutagenesis. Furthermore, several mutants that show different substrate specificity, such as F314E and V367W, were successfully designed by using the proposed small-molecule binding site as a model. F314E behaves as a highly selective aminopeptidase towards arginyl peptides with a selectivity increase of 850-fold, whereas V367W prefers alanyl peptides over arginyl peptides, just as the organic modulators do. |
| 语种 | 英语 |
| WOS记录号 | WOS:000278482200014 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/69953]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Lai, Luhua |
| 作者单位 | 1.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, Beijing Natl Lab Mol Sci, Beijing 100871, Peoples R China 2.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Xiaolu,Zhou, Lu,Wu, Yiran,et al. Modulating the Substrate Specificity of LTA4H Aminopeptidase by Using Chemical Compounds and Small-Molecule-Guided Mutagenesis[J]. CHEMBIOCHEM,2010,11(8):1120-1128. |
| APA | Jiang, Xiaolu.,Zhou, Lu.,Wu, Yiran.,Wei, Dengguo.,Sun, Chunyi.,...&Lai, Luhua.(2010).Modulating the Substrate Specificity of LTA4H Aminopeptidase by Using Chemical Compounds and Small-Molecule-Guided Mutagenesis.CHEMBIOCHEM,11(8),1120-1128. |
| MLA | Jiang, Xiaolu,et al."Modulating the Substrate Specificity of LTA4H Aminopeptidase by Using Chemical Compounds and Small-Molecule-Guided Mutagenesis".CHEMBIOCHEM 11.8(2010):1120-1128. |
入库方式： OAI收割
来源：化学研究所
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