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| {{STRUCTURE_1q32| PDB=1q32 | SCENE= }} | | {{STRUCTURE_1q32| PDB=1q32 | SCENE= }} |
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| '''Crystal Structure Analysis of the Yeast Tyrosyl-DNA Phosphodiesterase'''
| | ===Crystal Structure Analysis of the Yeast Tyrosyl-DNA Phosphodiesterase=== |
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| ==Overview==
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| Tyrosyl-DNA phosphodiesterase 1 (Tdp1) catalyzes the resolution of 3' and 5' phospho-DNA adducts. A defective mutant, associated with the recessive neurodegenerative disease SCAN1, accumulates Tdp1-DNA complexes in vitro. To assess the conservation of enzyme architecture, a 2.0 A crystal structure of yeast Tdp1 was determined that is very similar to human Tdp1. Poorly conserved regions of primary structure are peripheral to an essentially identical catalytic core. Enzyme mechanism was also conserved, because the yeast SCAN1 mutant (H(432)R) enhanced cell sensitivity to the DNA topoisomerase I (Top1) poison camptothecin. A more severe Top1-dependent lethality of Tdp1H(432)N was drug-independent, coinciding with increased covalent Top1-DNA and Tdp1-DNA complex formation in vivo. However, both H(432) mutants were recessive to wild-type Tdp1. Thus, yeast H(432) acts in the general acid/base catalytic mechanism of Tdp1 to resolve 3' phosphotyrosyl and 3' phosphoamide linkages. However, the distinct pattern of mutant Tdp1 activity evident in yeast cells, suggests a more severe defect in Tdp1H(432)N-catalyzed resolution of 3' phospho-adducts.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17707402}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17707402 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17707402}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transcription]] | | [[Category: Transcription]] |
| [[Category: Tyrosyl-dna phosphodiesterase]] | | [[Category: Tyrosyl-dna phosphodiesterase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:53:29 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:17:29 2008'' |
