1lpq: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
New page: left|200px<br /> <applet load="1lpq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lpq, resolution 3.14Å" /> '''Human DNA Topoisome...
 
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(17 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1lpq.gif|left|200px]]<br />
<applet load="1lpq" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1lpq, resolution 3.14&Aring;" />
'''Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion'''<br />


==Overview==
==Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion==
7,8-Dihydro-8-oxoguanine (8-oxoG) is the most common form of oxidative DNA, damage in human cells. Biochemical studies have shown that 8-oxoG, decreases the DNA cleavage activity of human topoisomerase I, an enzyme, vital to DNA metabolism and stability. We present the 3.1-A crystal, structure of human topoisomerase I in noncovalent complex with a DNA, oligonucleotide containing 8-oxoG at the +1 position in the scissile, strand. We find that 8-oxoG reorganizes the active site of human, topoisomerase I into an inactive conformation relative to the structures, of topoisomerase I-DNA complexes elucidated previously. The catalytic, Tyr-723-Phe rotates away from the DNA cleavage site and packs into the, body of the molecule. A second active-site residue, Arg-590, becomes, disordered and is not observed in the structure. The docked, inactive, conformation of Tyr-723-Phe is reminiscent of the related tyrosine, recombinase family of integrases and recombinases, suggesting a common, regulatory mechanism. We propose that human topoisomerase I binds to DNA, first in an inactive conformation and then rearranges its active site for, catalysis. 8-OxoG appears to impact topoisomerase I by stabilizing the, inactive, DNA-bound state.
<StructureSection load='1lpq' size='340' side='right'caption='[[1lpq]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lpq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LPQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LPQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lpq OCA], [https://pdbe.org/1lpq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lpq RCSB], [https://www.ebi.ac.uk/pdbsum/1lpq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lpq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TOP1_HUMAN TOP1_HUMAN] Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.
== Function ==
[https://www.uniprot.org/uniprot/TOP1_HUMAN TOP1_HUMAN] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:2833744</ref> <ref>PMID:19168442</ref> <ref>PMID:14594810</ref> <ref>PMID:16033260</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lp/1lpq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1lpq ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known disease associated with this structure: DNA topoisomerase I, camptothecin-resistant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126420 126420]]
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1LPQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LPQ OCA].
__TOC__
 
</StructureSection>
==Reference==
8-Oxoguanine rearranges the active site of human topoisomerase I., Lesher DT, Pommier Y, Stewart L, Redinbo MR, Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12102-7. Epub 2002 Sep 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12209008 12209008]
[[Category: DNA topoisomerase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Lesher, D.T.]]
[[Category: Lesher DT]]
[[Category: Pommier, Y.]]
[[Category: Pommier Y]]
[[Category: Redinbo, M.R.]]
[[Category: Redinbo MR]]
[[Category: Stewart, L.]]
[[Category: Stewart L]]
[[Category: dna damage]]
[[Category: induced conformational change]]
[[Category: protein-dna complex]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:03:21 2007''

Latest revision as of 07:34, 14 February 2024

Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion

1lpq, resolution 3.14Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=1lpq&oldid=4050845"