1k4s

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[[Image:1k4s.gif|left|200px]]
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{{STRUCTURE_1k4s| PDB=1k4s | SCENE= }}
{{STRUCTURE_1k4s| PDB=1k4s | SCENE= }}
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'''HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX'''
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===HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12426403 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12426403}}
==About this Structure==
==About this Structure==
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[[Category: Dna]]
[[Category: Dna]]
[[Category: Topoisomerase i]]
[[Category: Topoisomerase i]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:18:25 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 09:46:30 2008''

Revision as of 06:46, 2 July 2008

Image:1k4s.png

Template:STRUCTURE 1k4s

HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX

Template:ABSTRACT PUBMED 12426403

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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