中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
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
DOI10.1002/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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