1rg2
From Proteopedia
(New page: 200px<br /> <applet load="1rg2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rg2, resolution 2.10Å" /> '''Crystal structure o...) |
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| - | [[Image:1rg2.gif|left|200px]]<br /> | + | [[Image:1rg2.gif|left|200px]]<br /><applet load="1rg2" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1rg2, resolution 2.10Å" /> | caption="1rg2, resolution 2.10Å" /> | ||
'''Crystal structure of human Tyrosyl-DNA Phosphodiesterase complexed with vanadate, octopamine, and tetranucleotide AGTA'''<br /> | '''Crystal structure of human Tyrosyl-DNA Phosphodiesterase complexed with vanadate, octopamine, and tetranucleotide AGTA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of a | + | Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of a phosphodiester bond between a tyrosine residue and a DNA 3' phosphate and functions as a DNA repair enzyme that cleaves stalled topoisomerase I-DNA complexes. We previously determined a procedure to crystallize a quaternary complex containing Tdp1, vanadate, a DNA oligonucleotide, and a tyrosine-containing peptide that mimics the transition state for hydrolysis of the Tdp1 substrate. Here, the ability of vanadate to accept a variety of different ligands is exploited to produce several different quaternary complexes with a variety of oligonucleotides, and peptides or a tyrosine analogue, in efforts to explore the binding properties of the Tdp1 DNA and peptide binding clefts. Eight crystal structures of Tdp1 with vanadate, oligonucleotides, and peptides or peptide analogues were determined. These structures demonstrated that Tdp1 is able to bind substituents with limited sequence variation in the polypeptide moiety and also bind oligonucleotides with sequence variation at the 3' end. Additionally, the tyrosine analogue octopamine can replace topoisomerase I derived peptides as the apical ligand to vanadate. The versatility of this system suggests that the formation of quaternary complexes around vanadate could be adapted to become a useful method for structure-based inhibitor design and has the potential to be generally applicable to other enzymes that perform chemistry on phosphate esters. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1RG2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with VO4, SPM, OTS and OTR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1RG2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=VO4:'>VO4</scene>, <scene name='pdbligand=SPM:'>SPM</scene>, <scene name='pdbligand=OTS:'>OTS</scene> and <scene name='pdbligand=OTR:'>OTR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RG2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Champoux, J | + | [[Category: Champoux, J J.]] |
| - | [[Category: Davies, D | + | [[Category: Davies, D R.]] |
| - | [[Category: Hol, W | + | [[Category: Hol, W G.]] |
[[Category: Interthal, H.]] | [[Category: Interthal, H.]] | ||
[[Category: OTR]] | [[Category: OTR]] | ||
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[[Category: vanadate complex]] | [[Category: vanadate complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:50:31 2008'' |
Revision as of 12:50, 21 February 2008
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Crystal structure of human Tyrosyl-DNA Phosphodiesterase complexed with vanadate, octopamine, and tetranucleotide AGTA
Contents |
Overview
Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of a phosphodiester bond between a tyrosine residue and a DNA 3' phosphate and functions as a DNA repair enzyme that cleaves stalled topoisomerase I-DNA complexes. We previously determined a procedure to crystallize a quaternary complex containing Tdp1, vanadate, a DNA oligonucleotide, and a tyrosine-containing peptide that mimics the transition state for hydrolysis of the Tdp1 substrate. Here, the ability of vanadate to accept a variety of different ligands is exploited to produce several different quaternary complexes with a variety of oligonucleotides, and peptides or a tyrosine analogue, in efforts to explore the binding properties of the Tdp1 DNA and peptide binding clefts. Eight crystal structures of Tdp1 with vanadate, oligonucleotides, and peptides or peptide analogues were determined. These structures demonstrated that Tdp1 is able to bind substituents with limited sequence variation in the polypeptide moiety and also bind oligonucleotides with sequence variation at the 3' end. Additionally, the tyrosine analogue octopamine can replace topoisomerase I derived peptides as the apical ligand to vanadate. The versatility of this system suggests that the formation of quaternary complexes around vanadate could be adapted to become a useful method for structure-based inhibitor design and has the potential to be generally applicable to other enzymes that perform chemistry on phosphate esters.
Disease
Known disease associated with this structure: Spinocerebellar ataxia, autosomal recessive with axonal neuropathy OMIM:[607198]
About this Structure
1RG2 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes., Davies DR, Interthal H, Champoux JJ, Hol WG, J Med Chem. 2004 Feb 12;47(4):829-37. PMID:14761185
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