1nop
From Proteopedia
(New page: 200px<br /><applet load="1nop" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nop, resolution 2.30Å" /> '''Crystal structure of...) |
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| - | [[Image:1nop.gif|left|200px]]<br /><applet load="1nop" size=" | + | [[Image:1nop.gif|left|200px]]<br /><applet load="1nop" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1nop, resolution 2.30Å" /> | caption="1nop, resolution 2.30Å" /> | ||
'''Crystal structure of human tyrosyl-DNA phosphodiesterase (Tdp1) in complex with vanadate, DNA and a human topoisomerase I-derived peptide'''<br /> | '''Crystal structure of human tyrosyl-DNA phosphodiesterase (Tdp1) in complex with vanadate, DNA and a human topoisomerase I-derived peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Tyrosyl-DNA phosphodiesterase (Tdp1) is a member of the phospholipase D | + | Tyrosyl-DNA phosphodiesterase (Tdp1) is a member of the phospholipase D superfamily and acts as a DNA repair enzyme that removes stalled topoisomerase I- DNA complexes by hydrolyzing the bond between a tyrosine side chain and a DNA 3' phosphate. Despite the complexity of the substrate of this phosphodiesterase, vanadate succeeded in linking human Tdp1, a tyrosine-containing peptide, and a single-stranded DNA oligonucleotide into a quaternary complex that mimics the transition state for the first step of the catalytic reaction. The conformation of the bound substrate mimic gives compelling evidence that the topoisomerase I-DNA complex must undergo extensive modification prior to cleavage by Tdp1. The structure also illustrates that the use of vanadate as the central moiety in high-order complexes has the potential to be a general method for capturing protein-substrate interactions for phosphoryl transfer enzymes, even when the substrates are large, complicated, and unusual. |
==About this Structure== | ==About this Structure== | ||
| - | 1NOP 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 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1NOP 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> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NOP 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.J.]] |
[[Category: Interthal, H.]] | [[Category: Interthal, H.]] | ||
[[Category: VO4]] | [[Category: VO4]] | ||
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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 14:08:21 2008'' |
Revision as of 12:08, 21 February 2008
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Crystal structure of human tyrosyl-DNA phosphodiesterase (Tdp1) in complex with vanadate, DNA and a human topoisomerase I-derived peptide
Overview
Tyrosyl-DNA phosphodiesterase (Tdp1) is a member of the phospholipase D superfamily and acts as a DNA repair enzyme that removes stalled topoisomerase I- DNA complexes by hydrolyzing the bond between a tyrosine side chain and a DNA 3' phosphate. Despite the complexity of the substrate of this phosphodiesterase, vanadate succeeded in linking human Tdp1, a tyrosine-containing peptide, and a single-stranded DNA oligonucleotide into a quaternary complex that mimics the transition state for the first step of the catalytic reaction. The conformation of the bound substrate mimic gives compelling evidence that the topoisomerase I-DNA complex must undergo extensive modification prior to cleavage by Tdp1. The structure also illustrates that the use of vanadate as the central moiety in high-order complexes has the potential to be a general method for capturing protein-substrate interactions for phosphoryl transfer enzymes, even when the substrates are large, complicated, and unusual.
About this Structure
1NOP is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide., Davies DR, Interthal H, Champoux JJ, Hol WG, Chem Biol. 2003 Feb;10(2):139-47. PMID:12618186
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