| Conversion of human alpha-lactalbumin to an apo-like state in the complexes with basic poly-amino acids: toward understanding of the molecular mechanism of antitumor action of HAMLET. | |
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MedLine Citation:
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PMID: 15822935 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It was recently shown that alpha-lactalbumin associated with oleic acid (HAMLET) interacts with core histones thereby triggering apoptosis of tumor cells (J. Biol. Chem. 2003, 278, 42131). In previous work, we revealed that monomeric alpha-lactalbumin in the absence of fatty acids can also interact with histones and, moreover, with basic poly-amino acids (poly-Lys and poly-Arg) that represent simple models of histone proteins (Biochemistry 2004, 43, 5575). Association of alpha-lactalbumin with histone or poly-Lys(Arg) essentially changes its properties. In the present work, the character of the changes in structural properties and conformational stability of alpha-lactalbumin in the complex with poly-Lys(Arg) has been studied in detail by steady-state fluorescence, circular dichroism, and differential scanning calorimetry. Complex formation strongly depends on ionic strength, confirming its electrostatic nature. Experiments with the poly-amino acids of various molecular masses demonstrated a direct proportionality between the number of alpha-lactalbumin molecules bound per poly-Lys(Arg) and the surface area of the poly-amino acid random coil. The binding of the poly-amino acids to Ca2+-saturated human alpha-lactalbumin decreases its thermal stability down to the level of its free apo-form and decreases Ca2+-affinity by 4 orders of magnitude. The conformational state of alpha-lactalbumin in a complex with poly-Lys(Arg), named alpha-LActalbumin Modified by Poly-Amino acid (LAMPA), differs from all other alpha-lactalbumin states characterized to date, representing an apo-like (molten globule-like) state with substantially decreased affinity for calcium ion. The requirement for efficient conversion of alpha-lactalbumin to the LAMPA state is a poly-Lys(Arg) chain consisting of several tens of amino acid residues. |
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Authors:
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Serge E Permyakov; Irina V Pershikova; Andrei P Zhadan; John Goers; Anush G Bakunts; Vladimir N Uversky; Lawrence J Berliner; Eugene A Permyakov |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of proteome research Volume: 4 ISSN: 1535-3893 ISO Abbreviation: J. Proteome Res. Publication Date: 2005 Mar-Apr |
Date Detail:
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Created Date: 2005-04-12 Completed Date: 2005-07-28 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 101128775 Medline TA: J Proteome Res Country: United States |
Other Details:
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Languages: eng Pagination: 564-9 Citation Subset: IM |
Affiliation:
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Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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chemistry* Antineoplastic Agents / chemistry* Calorimetry / methods* Circular Dichroism Humans Lactalbumin / chemistry* Oleic Acid / chemistry* Spectrometry, Fluorescence Spectrophotometry, Ultraviolet |
| Grant Support | |
ID/Acronym/Agency:
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NIH GM 56970/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Antineoplastic Agents; 112-80-1/Oleic Acid; 9013-90-5/Lactalbumin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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