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| - | [[Image:2ugi.jpg|left|200px]] | |
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| - | {{Structure
| + | ==PROTEIN MIMICRY OF DNA FROM CRYSTAL STRUCTURES OF THE URACIL GLYCOSYLASE INHIBITOR PROTEIN AND ITS COMPLEX WITH ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE== |
| - | |PDB= 2ugi |SIZE=350|CAPTION= <scene name='initialview01'>2ugi</scene>, resolution 2.2Å
| + | <StructureSection load='2ugi' size='340' side='right'caption='[[2ugi]], [[Resolution|resolution]] 2.20Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene> | + | <table><tr><td colspan='2'>[[2ugi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_phage_PBS2 Bacillus phage PBS2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UGI FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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=2ugi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ugi OCA], [https://pdbe.org/2ugi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ugi RCSB], [https://www.ebi.ac.uk/pdbsum/2ugi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ugi ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [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. |
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| - | '''PROTEIN MIMICRY OF DNA FROM CRYSTAL STRUCTURES OF THE URACIL GLYCOSYLASE INHIBITOR PROTEIN AND ITS COMPLEX WITH ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE'''
| + | ==See Also== |
| - | | + | *[[Uracil glycosylase inhibitor|Uracil glycosylase inhibitor]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | 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. | + | [[Category: Bacillus phage PBS2]] |
| - | | + | [[Category: Large Structures]] |
| - | ==About this Structure==
| + | [[Category: Arvai AS]] |
| - | 2UGI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Phage_pbs1 Phage pbs1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UGI OCA].
| + | [[Category: Mol CD]] |
| - | | + | [[Category: Putnam CD]] |
| - | ==Reference==
| + | [[Category: 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., 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:[http://www.ncbi.nlm.nih.gov/pubmed/10080896 10080896]
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| - | [[Category: Phage pbs1]] | + | |
| - | [[Category: Single protein]] | + | |
| - | [[Category: Arvai, A S.]] | + | |
| - | [[Category: Mol, C D.]] | + | |
| - | [[Category: Putnam, C D.]] | + | |
| - | [[Category: Tainer, J A.]] | + | |
| - | [[Category: IMD]]
| + | |
| - | [[Category: protein inhibitor]]
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| - | [[Category: protein mimicry of dna]]
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:39:38 2008''
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