1k4t: Difference between revisions

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[[Image:1k4t.gif|left|200px]]<br /><applet load="1k4t" size="350" color="white" frame="true" align="right" spinBox="true"
[[Image:1k4t.gif|left|200px]]
caption="1k4t, resolution 2.10&Aring;" />
 
'''HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX'''<br />
{{Structure
|PDB= 1k4t |SIZE=350|CAPTION= <scene name='initialview01'>1k4t</scene>, resolution 2.10&Aring;
|SITE=
|LIGAND= <scene name='pdbligand=TTC:(S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3',4':6,7]INOLIZINO[1,2-B]-QUINOLINE-3,14(4H,12H)-DIONE'>TTC</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=TTG:2-(1-DIMETHYLAMINOMETHYL-2-HYDROXY-8-HYDROXYMETHYL-9-OXO-9,11-DIHYDRO-INDOLIZINO[1,2-B]QUINOLIN-7-YL)-2-HYDROXY-BUTYRIC+ACID'>TTG</scene> and <scene name='pdbligand=PG4:TETRAETHYLENE GLYCOL'>PG4</scene>
|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 (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX'''
 


==Overview==
==Overview==
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==About this Structure==
==About this Structure==
1K4T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=TTC:'>TTC</scene>, <scene name='pdbligand=HG:'>HG</scene>, <scene name='pdbligand=TTG:'>TTG</scene> and <scene name='pdbligand=PG4:'>PG4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1K4T OCA].  
1K4T 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=1K4T 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://ispc.weizmann.ac.il//pmbin/getpm?pmid=12426403 12426403]
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 Feb 21 13:30:10 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:12:36 2008''

Revision as of 13:12, 20 March 2008

File:1k4t.gif


PDB ID 1k4t

Drag the structure with the mouse to rotate
, resolution 2.10Å
Ligands: , , and
Activity: DNA topoisomerase, with EC number 5.99.1.2
Coordinates: save as pdb, mmCIF, xml



HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX


OverviewOverview

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.

DiseaseDisease

Known disease associated with this structure: DNA topoisomerase I, camptothecin-resistant OMIM:[126420]

About this StructureAbout this Structure

1K4T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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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