Document Detail


Turning a scorpion toxin into an antitumor miniprotein.
MedLine Citation:
PMID:  18798622     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53 and are important molecular targets for anticancer therapy. Grafting four residues of p53 critical for MDM2/MDMX binding to the N-terminal alpha-helix of BmBKTx1, a scorpion toxin isolated from the venom of the Asian scorpion Buthus martensi Karsch, converts the miniature protein into an effective inhibitor of p53 interactions with MDM2 and MDMX. Additional mutations enable the 27-residue miniprotein inhibitor to traverse the cell membrane and selectively kill tumor cells in a p53 dependent manner.
Authors:
Chong Li; Min Liu; Juahdi Monbo; Guozhang Zou; Changqing Li; Weirong Yuan; Davide Zella; Wei-Yue Lu; Wuyuan Lu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-18
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  130     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-08     Completed Date:  2008-12-17     Revised Date:  2009-01-22    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13546-8     Citation Subset:  IM    
Affiliation:
Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, Maryland 21201, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antineoplastic Agents / chemistry*
Models, Molecular
Protein Structure, Tertiary
Scorpion Venoms / chemistry*
Scorpions / chemistry*
Structural Homology, Protein
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Scorpion Venoms

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


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