Document Detail

Structural homology between DNA binding sites of DNA polymerase beta and DNA topoisomerase II.
MedLine Citation:
PMID:  11090281     Owner:  NLM     Status:  MEDLINE    
Unsaturated long-chain fatty acids selectively bind to the DNA binding sites of DNA polymerase beta and DNA topoisomerase II, and inhibit their activities, although the amino acid sequences of these enzymes are markedly different from each other. Computer modeling analysis revealed that the fatty acid interaction interface in both enzymes has a group of four amino acid residues in common, forming a pocket which binds to the fatty acid molecule. The four amino acid residues were Thr596, His735, Leu741 and Lys983 for yeast DNA topoisomerase II, corresponding to Thr79, His51, Leu11 and Lys35 for rat DNA polymerase beta. Using three-dimensional structure model analysis, we determined the spatial positioning of specific amino acid residues binding to the fatty acids in DNA topoisomerase II, and subsequently obtained supplementary information to build the structural model.
Y Mizushina; F Sugawara; A Iida; K Sakaguchi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular biology     Volume:  304     ISSN:  0022-2836     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2000-12-15     Completed Date:  2000-12-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  385-95     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Applied Biological Science, Science University of Tokyo, Noda, Chiba, 278-8510, Japan.
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MeSH Terms
Amino Acid Sequence
Binding Sites
Computer Simulation*
DNA / metabolism
DNA Polymerase beta / antagonists & inhibitors,  chemistry*,  metabolism*
DNA Topoisomerases, Type II / antagonists & inhibitors,  chemistry*,  metabolism*
Fatty Acids, Monounsaturated / metabolism
Fatty Acids, Unsaturated / metabolism*
Linoleic Acid / metabolism
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Structure, Tertiary
Sequence Alignment
Surface Plasmon Resonance
Yeasts / enzymology
Reg. No./Substance:
0/Fatty Acids, Monounsaturated; 0/Fatty Acids, Unsaturated; 2197-37-7/Linoleic Acid; 506-37-6/nervonic acid; 9007-49-2/DNA; EC 2.7.7.-/DNA Polymerase beta; EC Topoisomerases, Type II

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