1ois
From Proteopedia
(New page: 200px<br /><applet load="1ois" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ois, resolution 1.9Å" /> '''YEAST DNA TOPOISOMERA...) |
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| - | [[Image:1ois.gif|left|200px]]<br /><applet load="1ois" size=" | + | [[Image:1ois.gif|left|200px]]<br /><applet load="1ois" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ois, resolution 1.9Å" /> | caption="1ois, resolution 1.9Å" /> | ||
'''YEAST DNA TOPOISOMERASE I, N-TERMINAL FRAGMENT'''<br /> | '''YEAST DNA TOPOISOMERASE I, N-TERMINAL FRAGMENT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Type I DNA topoisomerases, divided mechanistically into two | + | BACKGROUND: Type I DNA topoisomerases, divided mechanistically into two subfamilies, are ubiquitous enzymes that participate in replication and transcription. In addition to its role in these fundamental processes, the biological importance of eukaryotic DNA topoisomerase I is underscored by its identification as the target of the antitumor alkaloid camptothecin. An understanding of the mechanism of catalysis and interactions with camptothecin and other drugs has been hampered by a lack of detailed structural information. RESULTS: The three-dimensional structure of a 26 kDA fragment (residues 135 to about 363) of Saccharomyces cerevisiae DNA topoisomerase I has been determined at 1.9 A resolution. The fragment has a novel architecture comprising a concave platform and a pair of outlying V-shaped helices. Photocrosslinking and protein footprinting experiments show that the positively charged concave surface and the junction region of the V-shaped pair of helices contact DNA in the enzyme-DNA complex. CONCLUSIONS: Crystallographic, biochemical and genetic data indicate that this 26 kDa fragment of yeast DNA topoisomerase I is involved in complex formation between the enzyme and DNA, and probably also in camptothecin-enzyme-DNA ternary complex formation. A molecular model for protein-DNA interaction based on these data is proposed. The bipartite DNA-binding regions of the 26 kDa fragment may enable eukaryotic DNA topoisomerase I to adapt to sequence-dependent structural variations in its DNA substrates. |
==About this Structure== | ==About this Structure== | ||
| - | 1OIS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Active as [http://en.wikipedia.org/wiki/DNA_topoisomerase DNA topoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.2 5.99.1.2] Full crystallographic information is available from [http:// | + | 1OIS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Active as [http://en.wikipedia.org/wiki/DNA_topoisomerase DNA topoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.2 5.99.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OIS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mondragon, A.]] | [[Category: Mondragon, A.]] | ||
[[Category: Sharma, A.]] | [[Category: Sharma, A.]] | ||
| - | [[Category: Wang, J | + | [[Category: Wang, J C.]] |
[[Category: dna-binding protein]] | [[Category: dna-binding protein]] | ||
[[Category: isomerase]] | [[Category: isomerase]] | ||
[[Category: topoisomerase]] | [[Category: topoisomerase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:18:16 2008'' |
Revision as of 12:18, 21 February 2008
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YEAST DNA TOPOISOMERASE I, N-TERMINAL FRAGMENT
Overview
BACKGROUND: Type I DNA topoisomerases, divided mechanistically into two subfamilies, are ubiquitous enzymes that participate in replication and transcription. In addition to its role in these fundamental processes, the biological importance of eukaryotic DNA topoisomerase I is underscored by its identification as the target of the antitumor alkaloid camptothecin. An understanding of the mechanism of catalysis and interactions with camptothecin and other drugs has been hampered by a lack of detailed structural information. RESULTS: The three-dimensional structure of a 26 kDA fragment (residues 135 to about 363) of Saccharomyces cerevisiae DNA topoisomerase I has been determined at 1.9 A resolution. The fragment has a novel architecture comprising a concave platform and a pair of outlying V-shaped helices. Photocrosslinking and protein footprinting experiments show that the positively charged concave surface and the junction region of the V-shaped pair of helices contact DNA in the enzyme-DNA complex. CONCLUSIONS: Crystallographic, biochemical and genetic data indicate that this 26 kDa fragment of yeast DNA topoisomerase I is involved in complex formation between the enzyme and DNA, and probably also in camptothecin-enzyme-DNA ternary complex formation. A molecular model for protein-DNA interaction based on these data is proposed. The bipartite DNA-binding regions of the 26 kDa fragment may enable eukaryotic DNA topoisomerase I to adapt to sequence-dependent structural variations in its DNA substrates.
About this Structure
1OIS is a Single protein structure of sequence from Saccharomyces cerevisiae. Active as DNA topoisomerase, with EC number 5.99.1.2 Full crystallographic information is available from OCA.
Reference
A 26 kDa yeast DNA topoisomerase I fragment: crystallographic structure and mechanistic implications., Lue N, Sharma A, Mondragon A, Wang JC, Structure. 1995 Dec 15;3(12):1315-22. PMID:8747458
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