1k4t: Difference between revisions
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{{STRUCTURE_1k4t| PDB=1k4t | SCENE= }} | {{STRUCTURE_1k4t| PDB=1k4t | SCENE= }} | ||
===HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX=== | |||
{{ABSTRACT_PUBMED_12426403}} | |||
=== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/TOP1_HUMAN TOP1_HUMAN]] Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98. | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/TOP1_HUMAN TOP1_HUMAN]] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:2833744</ref><ref>PMID:19168442</ref><ref>PMID:14594810</ref><ref>PMID:16033260</ref> | |||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
<ref group="xtra">PMID:012426403</ref><references group="xtra"/> | <ref group="xtra">PMID:012426403</ref><references group="xtra"/><references/> | ||
[[Category: DNA topoisomerase]] | [[Category: DNA topoisomerase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
Revision as of 06:02, 25 March 2013
HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEXHUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX
Template:ABSTRACT PUBMED 12426403
DiseaseDisease
[TOP1_HUMAN] Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.
FunctionFunction
[TOP1_HUMAN] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.[1][2][3][4]
About this StructureAbout this Structure
1k4t is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. Epub 2002 Nov 8. PMID:12426403 doi:10.1073/pnas.242259599
- ↑ D'Arpa P, Machlin PS, Ratrie H 3rd, Rothfield NF, Cleveland DW, Earnshaw WC. cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2543-7. PMID:2833744
- ↑ Eisenreich A, Bogdanov VY, Zakrzewicz A, Pries A, Antoniak S, Poller W, Schultheiss HP, Rauch U. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. Circ Res. 2009 Mar 13;104(5):589-99. doi: 10.1161/CIRCRESAHA.108.183905. Epub, 2009 Jan 22. PMID:19168442 doi:10.1161/CIRCRESAHA.108.183905
- ↑ Interthal H, Quigley PM, Hol WG, Champoux JJ. The role of lysine 532 in the catalytic mechanism of human topoisomerase I. J Biol Chem. 2004 Jan 23;279(4):2984-92. Epub 2003 Oct 31. PMID:14594810 doi:10.1074/jbc.M309959200
- ↑ Ioanoviciu A, Antony S, Pommier Y, Staker BL, Stewart L, Cushman M. Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA-enzyme-inhibitor complex as determined by X-ray crystallographic analysis. J Med Chem. 2005 Jul 28;48(15):4803-14. PMID:16033260 doi:10.1021/jm050076b