1q32
From Proteopedia
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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== | ||
| + | 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. | ||
==About this Structure== | ==About this Structure== | ||
1Q32 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q32 OCA]. | 1Q32 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q32 OCA]. | ||
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| + | ==Reference== | ||
| + | Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison., He X, van Waardenburg RC, Babaoglu K, Price AC, Nitiss KC, Nitiss JL, Bjornsti MA, White SW, J Mol Biol. 2007 Sep 28;372(4):1070-81. Epub 2007 Aug 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17707402 17707402] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: White, S W.]] | [[Category: White, S W.]] | ||
[[Category: Dna repair]] | [[Category: Dna repair]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Replication]] | ||
[[Category: Tdp]] | [[Category: Tdp]] | ||
| + | [[Category: Transcription]] | ||
[[Category: Tyrosyl-dna phosphodiesterase]] | [[Category: Tyrosyl-dna phosphodiesterase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:53:29 2008'' |
Revision as of 07:53, 11 June 2008
Crystal Structure Analysis of the Yeast Tyrosyl-DNA Phosphodiesterase
Overview
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.
About this Structure
1Q32 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison., He X, van Waardenburg RC, Babaoglu K, Price AC, Nitiss KC, Nitiss JL, Bjornsti MA, White SW, J Mol Biol. 2007 Sep 28;372(4):1070-81. Epub 2007 Aug 2. PMID:17707402 Page seeded by OCA on Wed Jun 11 10:53:29 2008
