1flz

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[[Image:1flz.jpg|left|200px]]
 
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{{Structure
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==URACIL DNA GLYCOSYLASE WITH UAAP==
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|PDB= 1flz |SIZE=350|CAPTION= <scene name='initialview01'>1flz</scene>, resolution 2.3&Aring;
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<StructureSection load='1flz' size='340' side='right'caption='[[1flz]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=URA:URACIL'>URA</scene>
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<table><tr><td colspan='2'>[[1flz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_B Escherichia coli B]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FLZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FLZ FirstGlance]. <br>
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|ACTIVITY= [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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=URA:URACIL'>URA</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1flz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1flz OCA], [https://pdbe.org/1flz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1flz RCSB], [https://www.ebi.ac.uk/pdbsum/1flz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1flz ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fl/1flz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1flz ConSurf].
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<div style="clear:both"></div>
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'''URACIL DNA GLYCOSYLASE WITH UAAP'''
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==See Also==
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*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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The DNA repair enzyme uracil DNA glycosylase (UDG) pinches the phosphodiester backbone of damaged DNA using the hydroxyl side chains of a conserved trio of serine residues, resulting in flipping of the deoxyuridine from the DNA helix into the enzyme active site. We have investigated the energetic role of these serine-phosphodiester interactions using the complementary approaches of crystallography, directed mutagenesis, and stereospecific phosphorothioate substitutions. A new crystal structure of UDG bound to 5'-HO-dUAAp-3' (which lacks the 5' phosphodiester group that interacts with the Ser88 pinching finger) shows that the glycosidic bond of dU has been cleaved, and that the enzyme has undergone the same specific clamping motion that brings key active site groups into position as previously observed in the structures of human UDG bound to large duplex DNA substrates. From this structure, it may be concluded that glycosidic bond cleavage and the induced fit conformational change in UDG can occur without the 5' pinching interaction. The S88A, S189A, and S192G "pinching" mutations exhibit 360-, 80-, and 21-fold damaging effects on k(cat)/K(m), respectively, while the S88A/S189A double mutant exhibits an 8200-fold damaging effect. A free energy analysis of the combined effects of nonbridging phosphorothioate substitution and mutation at these positions reveals the presence of a modest amount of strain energy between the compressed 5' and 3' phosphodiester groups flanking the bound uridine. Overall, these results indicate a role for these serine-phosphodiester interactions in uracil flipping and preorganization of the sugar ring into a reactive conformation. However, in contrast to a recent proposal [Parikh, S. S., et al. (2000) Proc Natl. Acad. Sci. 94, 5083], there is no evidence that conformational strain of the glycosidic bond induced by serine pinching plays a major role in the 10(12)-fold rate enhancement brought about by UDG.
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[[Category: Escherichia coli B]]
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[[Category: Large Structures]]
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==About this Structure==
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[[Category: Gilliland GL]]
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1FLZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FLZ OCA].
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[[Category: Gordley RG]]
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[[Category: Jagadeesh GJ]]
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==Reference==
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[[Category: Jiang YL]]
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Stressing-out DNA? The contribution of serine-phosphodiester interactions in catalysis by uracil DNA glycosylase., Werner RM, Jiang YL, Gordley RG, Jagadeesh GJ, Ladner JE, Xiao G, Tordova M, Gilliland GL, Stivers JT, Biochemistry. 2000 Oct 17;39(41):12585-94. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11027138 11027138]
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[[Category: Ladner JE]]
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[[Category: Escherichia coli]]
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[[Category: Stivers JT]]
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[[Category: Single protein]]
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[[Category: Tordova M]]
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[[Category: Uridine nucleosidase]]
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[[Category: Werner RM]]
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[[Category: Gilliland, G L.]]
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[[Category: Xiao G]]
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[[Category: Gordley, R G.]]
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[[Category: Jagadeesh, G J.]]
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[[Category: Jiang, Y L.]]
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[[Category: Ladner, J E.]]
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[[Category: Stivers, J T.]]
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[[Category: Tordova, M.]]
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[[Category: Werner, R M.]]
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[[Category: Xiao, G.]]
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[[Category: URA]]
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[[Category: glycosylase]]
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[[Category: hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:10:56 2008''
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Current revision

URACIL DNA GLYCOSYLASE WITH UAAP

PDB ID 1flz

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