This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1lpq
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="1lpq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lpq, resolution 3.14Å" /> '''Human DNA Topoisome...)
Next diff →
Revision as of 15:56, 12 November 2007
|
Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion
Contents |
Overview
7,8-Dihydro-8-oxoguanine (8-oxoG) is the most common form of oxidative DNA, damage in human cells. Biochemical studies have shown that 8-oxoG, decreases the DNA cleavage activity of human topoisomerase I, an enzyme, vital to DNA metabolism and stability. We present the 3.1-A crystal, structure of human topoisomerase I in noncovalent complex with a DNA, oligonucleotide containing 8-oxoG at the +1 position in the scissile, strand. We find that 8-oxoG reorganizes the active site of human, topoisomerase I into an inactive conformation relative to the structures, of topoisomerase I-DNA complexes elucidated previously. The catalytic, Tyr-723-Phe rotates away from the DNA cleavage site and packs into the, body of the molecule. A second active-site residue, Arg-590, becomes, disordered and is not observed in the structure. The docked, inactive, conformation of Tyr-723-Phe is reminiscent of the related tyrosine, recombinase family of integrases and recombinases, suggesting a common, regulatory mechanism. We propose that human topoisomerase I binds to DNA, first in an inactive conformation and then rearranges its active site for, catalysis. 8-OxoG appears to impact topoisomerase I by stabilizing the, inactive, DNA-bound state.
Disease
Known disease associated with this structure: DNA topoisomerase I, camptothecin-resistant OMIM:[126420]
About this Structure
1LPQ is a Single protein structure of sequence from Homo sapiens. Active as DNA topoisomerase, with EC number 5.99.1.2 Full crystallographic information is available from OCA.
Reference
8-Oxoguanine rearranges the active site of human topoisomerase I., Lesher DT, Pommier Y, Stewart L, Redinbo MR, Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12102-7. Epub 2002 Sep 3. PMID:12209008
Page seeded by OCA on Mon Nov 12 18:03:21 2007
