| http://purl.uniprot.org/citations/12209008 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12209008 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12209008 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.192282699"xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.192282699"xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Redinbo M.R."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Redinbo M.R."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Pommier Y."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Pommier Y."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Stewart L."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Stewart L."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Lesher D.T."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/author | "Lesher D.T."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/pages | "12102-12107"xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/pages | "12102-12107"xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/title | "8-Oxoguanine rearranges the active site of human topoisomerase I."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/title | "8-Oxoguanine rearranges the active site of human topoisomerase I."xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/volume | "99"xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://purl.uniprot.org/core/volume | "99"xsd:string |
| http://purl.uniprot.org/citations/12209008 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12209008 |
| http://purl.uniprot.org/citations/12209008 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12209008 |