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| | ==A comparative study of uracil DNA glycosylases from human and herpes simplex virus type 1== | | ==A comparative study of uracil DNA glycosylases from human and herpes simplex virus type 1== |
| - | <StructureSection load='2c56' size='340' side='right' caption='[[2c56]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='2c56' size='340' side='right'caption='[[2c56]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2c56]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-1 Hhv-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2C56 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2c56]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1 Human alphaherpesvirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C56 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SUC:SUCROSE'>SUC</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lau|1lau]], [[1udg|1udg]], [[1udh|1udh]], [[1udi|1udi]], [[2c53|2c53]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uridine_nucleosidase Uridine nucleosidase], with EC number [http://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=2c56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c56 OCA], [https://pdbe.org/2c56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c56 RCSB], [https://www.ebi.ac.uk/pdbsum/2c56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c56 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c56 OCA], [http://pdbe.org/2c56 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2c56 RCSB], [http://www.ebi.ac.uk/pdbsum/2c56 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2c56 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UNG_HHV11 UNG_HHV11]] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosine. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly, in terminally differentiated neurons which lack DNA repair enzymes.<ref>PMID:7552746</ref> <ref>PMID:16306042</ref> | + | [https://www.uniprot.org/uniprot/UNG_HHV11 UNG_HHV11] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosine. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly, in terminally differentiated neurons which lack DNA repair enzymes.<ref>PMID:7552746</ref> <ref>PMID:16306042</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hhv-1]] | + | [[Category: Human alphaherpesvirus 1]] |
| - | [[Category: Uridine nucleosidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Baldwin, G S]] | + | [[Category: Baldwin GS]] |
| - | [[Category: Bellamy, S R.W]] | + | [[Category: Bellamy SRW]] |
| - | [[Category: Carpenter, E P]] | + | [[Category: Carpenter EP]] |
| - | [[Category: Krusong, K]] | + | [[Category: Krusong K]] |
| - | [[Category: Savva, R]] | + | [[Category: Savva R]] |
| - | [[Category: Dna damage]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Glycosidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Uracil dna glycosylase]]
| + | |
| Structural highlights
Function
UNG_HHV11 Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosine. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly, in terminally differentiated neurons which lack DNA repair enzymes.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Uracil-DNA glycosylase (UNG) is the key enzyme responsible for initiation of base excision repair. We have used both kinetic and binding assays for comparative analysis of UNG enzymes from humans and herpes simplex virus type 1 (HSV-1). Steady-state fluorescence assays showed that hUNG has a much higher specificity constant (k(cat)/K(m)) compared with the viral enzyme due to a lower K(m). The binding of UNG to DNA was also studied using a catalytically inactive mutant of UNG and non-cleavable substrate analogs (2'-deoxypseudouridine and 2'-alpha-fluoro-2'-deoxyuridine). Equilibrium DNA binding revealed that both human and HSV-1 UNG enzymes bind to abasic DNA and both substrate analogs more weakly than to uracil-containing DNA. Structure determination of HSV-1 D88N/H210N UNG in complex with uracil revealed detailed information on substrate binding. Together, these results suggest that a significant proportion of the binding energy is provided by specific interactions with the target uracil. The kinetic parameters for human UNG indicate that it is likely to have activity against both U.A and U.G mismatches in vivo. Weak binding to abasic DNA also suggests that UNG activity is unlikely to be coupled to the subsequent common steps of base excision repair.
A comparative study of uracil-DNA glycosylases from human and herpes simplex virus type 1.,Krusong K, Carpenter EP, Bellamy SR, Savva R, Baldwin GS J Biol Chem. 2006 Feb 24;281(8):4983-92. Epub 2005 Nov 22. PMID:16306042[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Savva R, Pearl LH. Nucleotide mimicry in the crystal structure of the uracil-DNA glycosylase-uracil glycosylase inhibitor protein complex. Nat Struct Biol. 1995 Sep;2(9):752-7. PMID:7552746
- ↑ Krusong K, Carpenter EP, Bellamy SR, Savva R, Baldwin GS. A comparative study of uracil-DNA glycosylases from human and herpes simplex virus type 1. J Biol Chem. 2006 Feb 24;281(8):4983-92. Epub 2005 Nov 22. PMID:16306042 doi:http://dx.doi.org/10.1074/jbc.M509137200
- ↑ Krusong K, Carpenter EP, Bellamy SR, Savva R, Baldwin GS. A comparative study of uracil-DNA glycosylases from human and herpes simplex virus type 1. J Biol Chem. 2006 Feb 24;281(8):4983-92. Epub 2005 Nov 22. PMID:16306042 doi:http://dx.doi.org/10.1074/jbc.M509137200
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