3ogu: Difference between revisions
New page: '''Unreleased structure''' The entry 3ogu is ON HOLD Authors: Marx, A., Diederichs, K., Bergen, K. Description: DNA Polymerase beta mutant 5P20 complexed with 6bp of DNA ''Page seeded... |
No edit summary |
||
| (10 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==DNA Polymerase beta mutant 5P20 complexed with 6bp of DNA== | ||
<StructureSection load='3ogu' size='340' side='right'caption='[[3ogu]], [[Resolution|resolution]] 1.84Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ogu]] 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=3OGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OGU 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]] 1.845Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=3ogu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ogu OCA], [https://pdbe.org/3ogu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ogu RCSB], [https://www.ebi.ac.uk/pdbsum/3ogu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ogu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DPOLB_HUMAN DPOLB_HUMAN] Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.<ref>PMID:9207062</ref> <ref>PMID:9572863</ref> <ref>PMID:11805079</ref> <ref>PMID:21362556</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The DNA of every cell in the human body gets damaged more than 50,000 times a day. The most frequent damages are abasic sites. This kind of damage blocks proceeding DNA synthesis by several DNA polymerases that are involved in DNA replication and repair. The mechanistic basis for the incapability of these DNA polymerases to bypass abasic sites is not clarified. To gain insights into the mechanistic basis, we intended to identify amino acid residues that govern for the pausing of DNA polymerase beta when incorporating a nucleotide opposite to abasic sites. Human DNA polymerase beta was chosen because it is a well characterized DNA polymerase and serves as model enzyme for studies of DNA polymerase mechanisms. Moreover, it acts as the main gap-filling enzyme in base excision repair, and human tumor studies suggest a link between DNA polymerase beta and cancer. In this study we employed high throughput screening of a library of more than 11,000 human DNA polymerase beta variants. We identified two mutants that have increased ability to incorporate a nucleotide opposite to an abasic site. We found that the substitutions E232K and T233I promote incorporation opposite the lesion. In addition to this feature, the variants have an increased activity and a lower fidelity when processing nondamaged DNA. The mutations described in this work are located in well characterized regions but have not been reported before. A crystallographic structure of one of the mutants was obtained, providing structural insights. | |||
Human DNA polymerase beta mutations allowing efficient abasic site bypass.,Gieseking S, Bergen K, Di Pasquale F, Diederichs K, Welte W, Marx A J Biol Chem. 2011 Feb 4;286(5):4011-20. Epub 2010 Nov 24. PMID:21107011<ref>PMID:21107011</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ogu" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bergen K]] | |||
[[Category: Diederichs K]] | |||
[[Category: Marx A]] | |||