1k4s

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
[[Image:1k4s.gif|left|200px]]
[[Image:1k4s.gif|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 1k4s |SIZE=350|CAPTION= <scene name='initialview01'>1k4s</scene>, resolution 3.20&Aring;
+
The line below this paragraph, containing "STRUCTURE_1k4s", creates the "Structure Box" on the page.
-
|SITE=
+
You may change the PDB parameter (which sets the PDB file loaded into the applet)
-
|LIGAND= <scene name='pdbligand=5IU:5-IODO-2&#39;-DEOXYURIDINE-5&#39;-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SPT:5&#39;-THIO-THYMIDINE+PHOSPHONIC+ACID'>SPT</scene>
+
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-
|ACTIVITY= <span class='plainlinks'>[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] </span>
+
or leave the SCENE parameter empty for the default display.
-
|GENE=
+
-->
-
|DOMAIN=
+
{{STRUCTURE_1k4s| PDB=1k4s | SCENE= }}
-
|RELATEDENTRY=[[1a35|1A35]], [[1a31|1A31]], [[1a36|1A36]]
+
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1k4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k4s OCA], [http://www.ebi.ac.uk/pdbsum/1k4s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1k4s RCSB]</span>
+
-
}}
+
'''HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX'''
'''HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX'''
Line 32: Line 29:
[[Category: Staker, B L.]]
[[Category: Staker, B L.]]
[[Category: Stewart, L J.]]
[[Category: Stewart, L J.]]
-
[[Category: complex (isomerase/dna)]]
+
[[Category: Dna]]
-
[[Category: dna]]
+
[[Category: Topoisomerase i]]
-
[[Category: topoisomerase i]]
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:18:25 2008''
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:43:24 2008''
+

Revision as of 19:18, 2 May 2008

Image:1k4s.gif

Template:STRUCTURE 1k4s

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


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.

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 Page seeded by OCA on Fri May 2 22:18:25 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1k4s"
Personal tools