9lnp

From Proteopedia

(Difference between revisions)

Current revision

the hUNG bound to DNA product embedding uridine ribonucleotide

Structural highlights

9lnp is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.76Å
Ligands:	,
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.

Publication Abstract from PubMed

Uridine (rU) and 2'-deoxyuridine (dU) are common DNA lesions. dU is repaired through a base excision repair (BER) pathway initiated by uracil DNA glycosylase (UDG), while rU is typically removed from DNA via ribonucleotide excision repair, mediated by RNase H2. In this study, we report that rU is also repaired through the UDG-mediated BER pathway. We found that UDG catalyzes the removal of uracil from rU embedded in DNA, but exhibits no activity toward rU in RNA. Biochemical and crystallographic analyses revealed that the 2'-OH group of rU is effectively accommodated by UDG and directly participates in catalyzing the hydrolysis of the N-glycosidic bond. The abasic site product generated upon removal of uracil from rU by UDG is further processed by downstream BER enzymes to restore undamaged DNA. Our findings suggest that UDG-initiated BER constitutes a previously unrecognized pathway for the repair of rU-specific ribonucleotides. Additionally, we developed a method for selectively quantifying rU content in DNA. Using this method, we determined that rU repair by UDG is not a major pathway in human cells. This discovery expands our understanding of the diverse biological functions of UDG, and inspires further investigation to determine the role of its rU-removal in cells.

Uridine Embedded within DNA is Repaired by Uracil DNA Glycosylase via a Mechanism Distinct from That of Ribonuclease H2.,Fan C, Zhan X, Guo F, Li Q, Lu K, Shan X, Zhou Y, Ren M, Greenberg MM, Liu Y, Zhou C J Am Chem Soc. 2025 Apr 2;147(13):11574-11583. doi: 10.1021/jacs.5c01436. Epub , 2025 Mar 25. PMID:40130361^[3]

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
↑ Fan C, Zhan X, Guo F, Li Q, Lu K, Shan X, Zhou Y, Ren M, Greenberg MM, Liu Y, Zhou C. Uridine Embedded within DNA is Repaired by Uracil DNA Glycosylase via a Mechanism Distinct from That of Ribonuclease H2. J Am Chem Soc. 2025 Apr 2;147(13):11574-11583. PMID:40130361 doi:10.1021/jacs.5c01436

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9lnp"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9lnp is ON HOLD
+==the hUNG bound to DNA product embedding uridine ribonucleotide==
+<StructureSection load='9lnp' size='340' side='right'caption='[[9lnp]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9lnp]] 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=9LNP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LNP 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]] 1.76&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=RP5:5-O-PHOSPHONO-BETA-D-RIBOFURANOSE'>RP5</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=9lnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lnp OCA], [https://pdbe.org/9lnp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lnp RCSB], [https://www.ebi.ac.uk/pdbsum/9lnp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lnp 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Uridine (rU) and 2'-deoxyuridine (dU) are common DNA lesions. dU is repaired through a base excision repair (BER) pathway initiated by uracil DNA glycosylase (UDG), while rU is typically removed from DNA via ribonucleotide excision repair, mediated by RNase H2. In this study, we report that rU is also repaired through the UDG-mediated BER pathway. We found that UDG catalyzes the removal of uracil from rU embedded in DNA, but exhibits no activity toward rU in RNA. Biochemical and crystallographic analyses revealed that the 2'-OH group of rU is effectively accommodated by UDG and directly participates in catalyzing the hydrolysis of the N-glycosidic bond. The abasic site product generated upon removal of uracil from rU by UDG is further processed by downstream BER enzymes to restore undamaged DNA. Our findings suggest that UDG-initiated BER constitutes a previously unrecognized pathway for the repair of rU-specific ribonucleotides. Additionally, we developed a method for selectively quantifying rU content in DNA. Using this method, we determined that rU repair by UDG is not a major pathway in human cells. This discovery expands our understanding of the diverse biological functions of UDG, and inspires further investigation to determine the role of its rU-removal in cells.
-Authors:
+Uridine Embedded within DNA is Repaired by Uracil DNA Glycosylase via a Mechanism Distinct from That of Ribonuclease H2.,Fan C, Zhan X, Guo F, Li Q, Lu K, Shan X, Zhou Y, Ren M, Greenberg MM, Liu Y, Zhou C J Am Chem Soc. 2025 Apr 2;147(13):11574-11583. doi: 10.1021/jacs.5c01436. Epub , 2025 Mar 25. PMID:40130361<ref>PMID:40130361</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9lnp" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Fan C]]
+[[Category: Liu Y]]
+[[Category: Zhan X]]
+[[Category: Zhou C]]

9lnp

From Proteopedia

Current revision

the hUNG bound to DNA product embedding uridine ribonucleotide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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