1seu

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[[Image:1seu.gif|left|200px]]<br /><applet load="1seu" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1seu.gif|left|200px]]
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caption="1seu, resolution 3.00&Aring;" />
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'''Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex'''<br />
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{{Structure
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|PDB= 1seu |SIZE=350|CAPTION= <scene name='initialview01'>1seu</scene>, resolution 3.00&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SA3:2,10-DIHYDROXY-12-(BETA-D-GLUCOPYRANOSYL)-6,7,12,13-TETRAHYDROINDOLO[2,3-A]PYRROLO[3,4-C]CARBAZOLE-5,7-DIONE'>SA3</scene>
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|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]
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|GENE= TOP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1SEU 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=SA3:'>SA3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1SEU OCA].
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1SEU 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=1SEU OCA].
==Reference==
==Reference==
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Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex., Staker BL, Feese MD, Cushman M, Pommier Y, Zembower D, Stewart L, Burgin AB, J Med Chem. 2005 Apr 7;48(7):2336-45. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15801827 15801827]
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Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex., Staker BL, Feese MD, Cushman M, Pommier Y, Zembower D, Stewart L, Burgin AB, J Med Chem. 2005 Apr 7;48(7):2336-45. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15801827 15801827]
[[Category: DNA topoisomerase]]
[[Category: DNA topoisomerase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: topoisomerase i]]
[[Category: topoisomerase i]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:44 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:04:03 2008''

Revision as of 12:04, 20 March 2008

Image:1seu.gif


PDB ID 1seu

Drag the structure with the mouse to rotate
, resolution 3.00Å
Ligands:
Gene: TOP1 (Homo sapiens)
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 Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex


Contents

Overview

Human topoisomerase I (top1) is the molecular target of a diverse set of anticancer compounds, including the camptothecins, indolocarbazoles, and indenoisoquinolines. These compounds bind to a transient top1-DNA covalent complex and inhibit the resealing of a single-strand nick that the enzyme creates to relieve superhelical tension in duplex DNA. (Hertzberg, R. P.; et al. Biochem. 1989, 28, 4629-4638. Hsiang, Y. H.; et al. J. Biol. Chem 1985, 260, 14873-14878. Champoux, J. J. Annu. Rev. Biochem. 2001, 70, 369-413. Stewart, L.; et al. Science 1998, 729, 1534-1541.) We report the X-ray crystal structures of the human top1-DNA complex bound with camptothecin and representative members of the indenoisoquinoline and indolocarbazole classes of top1 poisons. The planar nature of all three structurally diverse classes allows them to intercalate between DNA base pairs at the site of single-strand cleavage. All three classes of compounds have a free electron pair near Arg364, a residue that if mutated confers resistance to all three classes of drugs. The common intercalative binding mode is augmented by unexpected chemotype-specific contacts with amino acid residues Asn352 and Glu356, which adopt alternative side-chain conformations to accommodate the bound compounds. These new X-ray structures explain how very different molecules can stabilize top1-DNA covalent complexes and will aid the rational design of completely novel structural classes of anticancer drugs.

Disease

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

About this Structure

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

Reference

Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex., Staker BL, Feese MD, Cushman M, Pommier Y, Zembower D, Stewart L, Burgin AB, J Med Chem. 2005 Apr 7;48(7):2336-45. PMID:15801827

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