1seu: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
Line 1: Line 1:
[[Image:1seu.gif|left|200px]]
{{Seed}}
[[Image:1seu.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1seu|  PDB=1seu  |  SCENE=  }}  
{{STRUCTURE_1seu|  PDB=1seu  |  SCENE=  }}  


'''Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex'''
===Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex===




==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.
The line below this paragraph, {{ABSTRACT_PUBMED_15801827}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 15801827 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_15801827}}


==Disease==
==Disease==
Line 37: Line 41:
[[Category: Poison]]
[[Category: Poison]]
[[Category: Topoisomerase i]]
[[Category: Topoisomerase i]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 08:37:10 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:21:19 2008''

Revision as of 02:21, 29 July 2008

File:1seu.png

Template:STRUCTURE 1seu

Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex

Template:ABSTRACT PUBMED 15801827

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

Page seeded by OCA on Tue Jul 29 05:21:19 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=1seu&oldid=728745"