This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

Sandbox reserved 1753

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 00:09, 10 October 2022

A NUCLEOTIDE-FLIPPING MECHANISM FROM THE STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO DNA

Structural highlights

4skn is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	Uridine nucleosidase, with EC number 3.2.2.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[UNG_HUMAN] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM: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.^[1] ^[2]

Function

[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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Introduction

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 removes and repairs damaged bases usually these are single-stranded DNA breaks. BER corrects DNA damage that results from small leisures that do not disrupt the double helix^[3].

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^[4].

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 ssDNA. So if a Uracil is found in dsDNA then that means the strand has been damaged and needs repair. When Uracil-DNA Glycosylase finds the site it binds to it. The of Uracil Glycosylase; D145, Y147, F158, N204, H268, L272 is what binds to the double-stranded DNA with the damaged lesion. Then a nucleotide-flipping mechanism flips the site of repair out of the double helix. The dsDNA has a 10bp that contains a U G base pair mismatch. This is what allows the and flip the damaged site out of the double helix. When flipped out of the helix takes its place in the minor groove since AP sites can be mutagenic^[5]. 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.

A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA., Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA Nature. 1996 Nov 7;384(6604):87-92. PMID:8900285^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Imai K, Slupphaug G, Lee WI, Revy P, Nonoyama S, Catalan N, Yel L, Forveille M, Kavli B, Krokan HE, Ochs HD, Fischer A, Durandy A. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol. 2003 Oct;4(10):1023-8. Epub 2003 Sep 7. PMID:12958596 doi:http://dx.doi.org/10.1038/ni974
↑ Kavli B, Andersen S, Otterlei M, Liabakk NB, Imai K, Fischer A, Durandy A, Krokan HE, Slupphaug G. B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. J Exp Med. 2005 Jun 20;201(12):2011-21. PMID:15967827 doi:10.1084/jem.20050042
↑ Schormann N, Ricciardi R, Chattopadhyay D. Uracil-DNA glycosylases-structural and functional perspectives on an essential family of DNA repair enzymes. Protein Sci. 2014 Dec;23(12):1667-85. doi: 10.1002/pro.2554. Epub 2014 Oct 25. PMID:25252105 doi:http://dx.doi.org/10.1002/pro.2554
↑ Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA. Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J. 1998 Sep 1;17(17):5214-26. PMID:9724657 doi:10.1093/emboj/17.17.5214
↑ Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA. A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature. 1996 Nov 7;384(6604):87-92. PMID:8900285 doi:http://dx.doi.org/10.1038/384087a0
↑ Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA. A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature. 1996 Nov 7;384(6604):87-92. PMID:8900285 doi:http://dx.doi.org/10.1038/384087a0

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Introduction
6 Function
7 Uracil-DNA Glycosylase
8 See Also
9 References

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_reserved_1753"

@@ Line 1: / Line 1: @@
+==A NUCLEOTIDE-FLIPPING MECHANISM FROM THE STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO DNA==
+<StructureSection load='4skn' size='340' side='right'caption='[[4skn]], [[Resolution|resolution]] 2.90&Aring;' 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;">
 == Introduction ==
 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 removes and repairs damaged bases usually these are single-stranded DNA breaks. BER corrects DNA damage that results from small leisures that do not disrupt the double helix<ref>PMID:25252105</ref>.

Sandbox reserved 1753

From Proteopedia

Revision as of 00:09, 10 October 2022

A NUCLEOTIDE-FLIPPING MECHANISM FROM THE STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO DNA

Structural highlights

Disease

Function

Evolutionary Conservation

Introduction

Function

Uracil-DNA Glycosylase

See Also

References

Contents

Views

Personal tools

Navigation

Search

Toolbox