Sandbox reserved 1753
From Proteopedia
(Difference between revisions)
| (27 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | + | ==DNA Repair Mechanism; URACIL-DNA GLYCOSYLASE== | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
<StructureSection load='4skn' size='340' side='right'caption='[[4skn]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='4skn' size='340' side='right'caption='[[4skn]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
| - | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4skn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4SKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4SKN FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=URA:URACIL'>URA</scene>, <scene name='pdbligand=ORP:2-DEOXY-5-PHOSPHONO-RIBOSE'>ORP</scene></td></tr> | ||
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Uridine_nucleosidase Uridine nucleosidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.3 3.2.2.3] </span></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=4skn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4skn OCA], [https://pdbe.org/4skn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4skn RCSB], [https://www.ebi.ac.uk/pdbsum/4skn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4skn ProSAT]</span></td></tr> | ||
| - | </table> | ||
| - | == Disease == | ||
| - | [[https://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN]] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:[https://omim.org/entry/608106 608106]]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.<ref>PMID:12958596</ref> <ref>PMID:15967827</ref> | ||
| - | == Function == | ||
| - | [[https://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN]] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. | ||
| - | == 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/sk/4skn_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=4skn ConSurf]. | ||
| - | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Any <scene name='92/927197/Uracil/3'>Uracil</scene> bases in DNA, a result of either misincorporation or deamination of cytosine, are removed by uracil-DNA glycosylase (UDG), one of the most efficient and specific of the base-excision DNA-repair enzymes. Crystal structures of human and viral UDGs complexed with free uracil have indicated that the enzyme binds an extrahelical uracil. Such binding of undamaged extrahelical bases has been seen in the structures of two bacterial methyltransferases and bacteriophage T4 endonuclease V. Here we characterize the DNA binding and kinetics of several engineered human UDG mutants and present the crystal structure of one of these, which to our knowledge represents the first structure of any eukaryotic DNA repair enzyme in complex with its damaged, target DNA. Electrostatic orientation along the UDG active site, insertion of an amino acid (residue 272) into the DNA through the minor groove, and compression of the DNA backbone flanking the uracil all result in the flipping-out of the damaged base from the DNA major groove, allowing specific recognition of its phosphate, deoxyribose and uracil moieties. Our structure thus provides a view of a productive complex specific for cleavage of uracil from DNA and also reveals the basis for the enzyme-assisted nucleotide flipping by this critical DNA-repair enzyme. | ||
| - | |||
== Introduction == | == Introduction == | ||
| - | Glycosylase is an enzyme. Its main function is in Base Excision Repair(BER) | + | Glycosylase is an enzyme. Its main function is in Base Excision Repair(BER). Base Excision Repair is a DNA repair mechanism that fixes the most common type of DNA damage. BER corrects DNA damage that occurs from oxidation and methylation. BER removes and repairs damaged bases usually these are single-stranded DNA breaks. It also corrects DNA damage that results from small leisures that do not disrupt the double helix<ref>PMID:25252105</ref>. |
| - | + | ||
| + | == Function == | ||
| + | Glycosylase does this by cleaving the glycosidic bond of the damaged nucleotide, leaving the Deoxyribose nucleotide with no base. The deoxyribose is then cleaved by AP endonuclease creating an AP site. The gap that is left is filled in through DNA Polymerase and DNA ligase<ref>PMID:9724657</ref>. | ||
| - | + | == Uracil-DNA Glycosylase == | |
| + | The structure of Glycosylase has a couple of different forms in terms of its general structure there is Adenine and Uracil Glycosylase. DNA Uracil-Glycosylase specifically looks for any Uracil in the double-stranded DNA. It looks for Uracil in dsDNA because uracil is only found in RNA. So if a Uracil is found in dsDNA then that means one of the strands has been damaged and needs repair. The dsDNA in the 3D model contains a U G base pair mismatch. When Uracil-DNA Glycosylase finds the <scene name='92/927197/Uracil/4'>Uracil</scene> site it binds to it. Then a nucleotide-flipping mechanism flips the site of repair out of the double helix. The<scene name='92/927197/Active_site/7'>Active Site</scene> of Uracil Glycosylase; D145, Y147, F158, N204, H268, L272 is what binds to the double-stranded DNA with the damaged lesion. This is what allows the <scene name='92/927197/Uracil_glycolysis_interaction/5'>Uracil_Glycosylase interaction</scene> and flipping of the damaged site out of the double helix. ASN 204 and HIS 268 are responsible for catalyzing the cleavage of the glycosidic bond. TYR 147, PHE 158, and ASN 204 all aid in Uracil excision and replacement with Thymine. When flipped the damaged bases out of the helix <scene name='92/927197/Arg_side_chain/1'>ARG 272 side chain</scene> takes its place in the minor groove since AP sites can be mutagenic<ref>PMID:8900285</ref>. The Uracil is then replaced with a Thymine. This is because Uracil and Thymine have identical base pairing properties. Thymine happens to have greater resistance to photochemical mutations which is why we see it in dsDNA and not Uracil. | ||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4skn" style="background-color:#fffaf0;"></div> | ||
| - | ==See Also== | ||
| - | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| - | __TOC__ | ||
| - | </StructureSection> | ||
| - | [[Category: Human]] | ||
| - | [[Category: Large Structures]] | ||
| - | [[Category: Uridine nucleosidase]] | ||
| - | [[Category: Arvai, A S]] | ||
| - | [[Category: Kavli, B]] | ||
| - | [[Category: Krokan, H E]] | ||
| - | [[Category: Mol, C D]] | ||
| - | [[Category: Slupphaug, G]] | ||
| - | [[Category: Tainer, J A]] | ||
| - | [[Category: Dna]] | ||
| - | [[Category: Dna base excision repair]] | ||
| - | [[Category: Dna glycosylase]] | ||
| - | [[Category: Hydrolase-dna complex]] | ||
| - | [[Category: Uracil]] | ||
Current revision
DNA Repair Mechanism; URACIL-DNA GLYCOSYLASE
| |||||||||||
