Document Detail


Peptides from purified soybean beta-conglycinin inhibit fatty acid synthase by interaction with the thioesterase catalytic domain.
MedLine Citation:
PMID:  20148945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fatty acid synthase (FAS) is uniquely expressed at high levels in cancer cells and adipose tissue. The objectives of this study were to identify, purify and validate soy FAS inhibitory peptides and to predict their binding modes. Soy peptides were isolated from hydrolysates of purified beta-conglycinin by co-immunoprecipitation and identified using LC-MS/MS. Three peptides, KNPQLR, EITPEKNPQLR and RKQEEDEDEEQQRE, inhibited FAS. The biological activity of these peptides was confirmed by their inhibitory activity against purified chicken FAS (IC(50) = 79, 27 and 16 mum, respectively) and a high correlation (r = -0.7) with lipid accumulation in 3T3-L1 adipocytes. The FAS inhibitory potency of soy peptides also correlated with their molecular mass, pI value and the number of negatively charged and hydrophilic residues. Molecular modeling predicted that the large FAS inhibitory peptides (EITPEKNPQLR and RKQEEDEDEEQQRE) bond to the thioesterase domain of human FAS with lower interaction energies (-442 and -353 kcal.mol(-1), respectively) than classical thioesterase inhibitors (Orlistat, -91 kcal.mol(-1) and C75, -51 kcal.mol(-1)). Docking studies suggested that soy peptides blocked the active site through interactions within the catalytic triad, the interface cavity and the hydrophobic groove in the human FAS thioesterase domain. FAS thioesterase inhibitory activities displayed by the synthetic soy peptides EITPEKNPQLR and RKQEEDEDEEQQRE (IC(50) = 10.1 +/- 1.6 and 10.7 +/- 4.4 mum, respectively) were higher than C75 (58.7 mum) but lower than Orlistat (0.9 mum). This is the first study to identify FAS inhibitory peptides from purified beta-conglycinin hydrolysates and predict their binding modes at the molecular level, leading to their possible use as nutraceuticals.
Authors:
Cristina Martinez-Villaluenga; Sanjeewa G Rupasinghe; Mary A Schuler; Elvira Gonzalez de Mejia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-02-08
Journal Detail:
Title:  The FEBS journal     Volume:  277     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-12     Completed Date:  2010-04-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1481-93     Citation Subset:  IM    
Affiliation:
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, IL, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antigens, Plant / chemistry,  metabolism*,  pharmacology*
Catalytic Domain
Cells, Cultured
Chickens
Enzyme Activation / drug effects*
Enzyme Inhibitors / chemistry,  metabolism*
Fatty Acid Synthetase Complex* / antagonists & inhibitors,  metabolism
Gas Chromatography-Mass Spectrometry
Globulins / chemistry,  metabolism*,  pharmacology*
Humans
Inhibitory Concentration 50
Models, Molecular
Molecular Sequence Data
Peptides / pharmacology*
Seed Storage Proteins / chemistry,  metabolism*,  pharmacology*
Soybean Proteins / chemistry,  metabolism*,  pharmacology*
Thiolester Hydrolases / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Antigens, Plant; 0/Enzyme Inhibitors; 0/Globulins; 0/Peptides; 0/Seed Storage Proteins; 0/Soybean Proteins; 0/beta-conglycinin protein, Glycine max; EC 3.1.2.-/Thiolester Hydrolases; EC 6.-/Fatty Acid Synthetase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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