1r49
From Proteopedia
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| - | [[Image:1r49.gif|left|200px]] | + | [[Image:1r49.gif|left|200px]] |
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| - | '''Human topoisomerase I (Topo70) double mutant K532R/Y723F''' | + | {{Structure |
| + | |PDB= 1r49 |SIZE=350|CAPTION= <scene name='initialview01'>1r49</scene>, resolution 3.13Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= TOP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Human topoisomerase I (Topo70) double mutant K532R/Y723F''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1R49 is a [ | + | 1R49 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R49 OCA]. |
==Reference== | ==Reference== | ||
| - | The role of lysine 532 in the catalytic mechanism of human topoisomerase I., Interthal H, Quigley PM, Hol WG, Champoux JJ, J Biol Chem. 2004 Jan 23;279(4):2984-92. Epub 2003 Oct 31. PMID:[http:// | + | The role of lysine 532 in the catalytic mechanism of human topoisomerase I., Interthal H, Quigley PM, Hol WG, Champoux JJ, J Biol Chem. 2004 Jan 23;279(4):2984-92. Epub 2003 Oct 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14594810 14594810] |
[[Category: DNA topoisomerase]] | [[Category: DNA topoisomerase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: topoisomerase i]] | [[Category: topoisomerase i]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:46:36 2008'' |
Revision as of 11:46, 20 March 2008
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| , resolution 3.13Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | TOP1 (Homo sapiens) | ||||||
| Activity: | DNA topoisomerase, with EC number 5.99.1.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human topoisomerase I (Topo70) double mutant K532R/Y723F
Contents |
Overview
Based on co-crystal structures of human topoisomerase I with bound DNA, Lys(532) makes a minor groove contact with the strongly preferred thymidine residue at the site of covalent attachment (-1 position). Replacement of Lys(532) with either arginine or alanine has essentially no effect on the sequence preference of the enzyme, indicating that this interaction is not required for the preference for a T at the -1 position. Although both the cleavage and religation activities of the K532R mutant enzyme are reduced, cleavage is reduced to a greater extent than religation. The reverse is true for the K532A mutant enzyme with religation so impaired that the nicked intermediate accumulates during plasmid relaxation assays. Consistent with the shift in the cleavage religation equilibrium toward cleavage for the K532A mutant enzyme, expression of the mutant enzyme in Saccharomyces cerevisiae is cytotoxic, and thus this mutant enzyme mimics the effects of the anticancer drug camptothecin. Cleavage assays with the mutant enzymes using an oligonucleotide containing a 5'-bridging phosphorothiolate indicate that Lys(532) functions as a general acid during cleavage to protonate the leaving 5'-oxygen. It is possible that the contact with the -1 base is important during catalysis to provide positional rigidity to the active site. The corresponding residues in the vaccinia virus topoisomerase and the tyrosine recombinases may have similar critical roles in catalysis.
Disease
Known disease associated with this structure: DNA topoisomerase I, camptothecin-resistant OMIM:[126420]
About this Structure
1R49 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The role of lysine 532 in the catalytic mechanism of human topoisomerase I., Interthal H, Quigley PM, Hol WG, Champoux JJ, J Biol Chem. 2004 Jan 23;279(4):2984-92. Epub 2003 Oct 31. PMID:14594810
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