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| | <StructureSection load='2uug' size='340' side='right'caption='[[2uug]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='2uug' size='340' side='right'caption='[[2uug]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2uug]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bppb2 Bppb2] and [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UUG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2uug]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_phage_PBS2 Bacillus phage PBS2] and [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UUG FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UNG ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI]), UGI ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10684 BPPB2])</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]] 2.6Å</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=2uug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uug OCA], [https://pdbe.org/2uug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uug RCSB], [https://www.ebi.ac.uk/pdbsum/2uug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uug ProSAT]</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=2uug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uug OCA], [https://pdbe.org/2uug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uug RCSB], [https://www.ebi.ac.uk/pdbsum/2uug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uug ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/UNG_ECOLI UNG_ECOLI]] 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.[HAMAP-Rule:MF_00148] [[https://www.uniprot.org/uniprot/UNGI_BPPB2 UNGI_BPPB2]] This protein binds specifically and reversibly to the host uracil-DNA glycosylase, preventing removal of uracil residues from PBS2 DNA by the host uracil-excision repair system.
| + | [https://www.uniprot.org/uniprot/UNG_ECOLI UNG_ECOLI] 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.[HAMAP-Rule:MF_00148] |
| | == 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: Bppb2]] | + | [[Category: Bacillus phage PBS2]] |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Uridine nucleosidase]]
| + | [[Category: Arvai AS]] |
| - | [[Category: Arvai, A S]] | + | [[Category: Mol CD]] |
| - | [[Category: Mol, C D]] | + | [[Category: Putnam CD]] |
| - | [[Category: Putnam, C D]] | + | [[Category: Tainer JA]] |
| - | [[Category: Tainer, J A]] | + | |
| - | [[Category: Dna base excision repair]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protein inhibitor]]
| + | |
| - | [[Category: Protein mimicry of dna]]
| + | |
| - | [[Category: Replication]]
| + | |
| Structural highlights
Function
UNG_ECOLI 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.[HAMAP-Rule:MF_00148]
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 (UDG), which is a critical enzyme in DNA base-excision repair that recognizes and removes uracil from DNA, is specifically and irreversably inhibited by the thermostable uracil-DNA glycosylase inhibitor protein (Ugi). A paradox for the highly specific Ugi inhibition of UDG is how Ugi can successfully mimic DNA backbone interactions for UDG without resulting in significant cross-reactivity with numerous other enzymes that possess DNA backbone binding affinity. High-resolution X-ray crystal structures of Ugi both free and in complex with wild-type and the functionally defective His187Asp mutant Escherichia coli UDGs reveal the detailed molecular basis for duplex DNA backbone mimicry by Ugi. The overall shape and charge distribution of Ugi most closely resembles a midpoint in a trajectory between B-form DNA and the kinked DNA observed in UDG:DNA product complexes. Thus, Ugi targets the mechanism of uracil flipping by UDG and appears to be a transition-state mimic for UDG-flipping of uracil nucleotides from DNA. Essentially all the exquisite shape, electrostatic and hydrophobic complementarity for the high-affinity UDG-Ugi interaction is pre-existing, except for a key flip of the Ugi Gln19 carbonyl group and Glu20 side-chain, which is triggered by the formation of the complex. Conformational changes between unbound Ugi and Ugi complexed with UDG involve the beta-zipper structural motif, which we have named for the reversible pairing observed between intramolecular beta-strands. A similar beta-zipper is observed in the conversion between the open and closed forms of UDG. The combination of extremely high levels of pre-existing structural complementarity to DNA binding features specific to UDG with key local conformational changes in Ugi resolves the UDG-Ugi paradox and suggests a potentially general structural solution to the formation of very high affinity DNA enzyme-inhibitor complexes that avoid cross- reactivity.
Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase.,Putnam CD, Shroyer MJ, Lundquist AJ, Mol CD, Arvai AS, Mosbaugh DW, Tainer JA J Mol Biol. 1999 Mar 26;287(2):331-46. PMID:10080896[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Putnam CD, Shroyer MJ, Lundquist AJ, Mol CD, Arvai AS, Mosbaugh DW, Tainer JA. Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase. J Mol Biol. 1999 Mar 26;287(2):331-46. PMID:10080896 doi:10.1006/jmbi.1999.2605
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