1k4s
From Proteopedia
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| - | [[Image:1k4s.gif|left|200px]] | + | [[Image:1k4s.gif|left|200px]] |
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| - | '''HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX''' | + | {{Structure |
| + | |PDB= 1k4s |SIZE=350|CAPTION= <scene name='initialview01'>1k4s</scene>, resolution 3.20Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1K4S is a [ | + | 1K4S is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4S OCA]. |
==Reference== | ==Reference== | ||
| - | The mechanism of topoisomerase I poisoning by a camptothecin analog., Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L, Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. Epub 2002 Nov 8. PMID:[http:// | + | The mechanism of topoisomerase I poisoning by a camptothecin analog., Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L, Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. Epub 2002 Nov 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12426403 12426403] |
[[Category: DNA topoisomerase]] | [[Category: DNA topoisomerase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: topoisomerase i]] | [[Category: topoisomerase i]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:12:34 2008'' |
Revision as of 10:12, 20 March 2008
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| , resolution 3.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Activity: | DNA topoisomerase, with EC number 5.99.1.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX
Contents |
Overview
We report the x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan. Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (-1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme-substrate complex, Topotecan acts as an uncompetitive inhibitor. The structure can explain several of the known structure-activity relationships of the camptothecin family of anticancer drugs and suggests that there are at least two classes of mutations that can produce a drug-resistant enzyme. The first class includes changes to residues that contribute to direct interactions with the drug, whereas a second class would alter interactions with the DNA and thereby destabilize the drug-binding site.
Disease
Known disease associated with this structure: DNA topoisomerase I, camptothecin-resistant OMIM:[126420]
About this Structure
1K4S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The mechanism of topoisomerase I poisoning by a camptothecin analog., Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L, Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. Epub 2002 Nov 8. PMID:12426403
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