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1emh

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(New page: 200px<br /> <applet load="1emh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1emh, resolution 1.8&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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[[Image:1emh.gif|left|200px]]<br />
 
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<applet load="1emh" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1emh, resolution 1.8&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO UNCLEAVED SUBSTRATE-CONTAINING DNA'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO UNCLEAVED SUBSTRATE-CONTAINING DNA==
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Enzymatic transformations of macromolecular substrates such as DNA repair, enzyme/DNA transformations are commonly interpreted primarily by, active-site functional-group chemistry that ignores their extensive, interfaces. Yet human uracil-DNA glycosylase (UDG), an archetypical enzyme, that initiates DNA base-excision repair, efficiently excises the damaged, base uracil resulting from cytosine deamination even when active-site, functional groups are deleted by mutagenesis. The 1.8-A resolution, substrate analogue and 2.0-A resolution cleaved product cocrystal, structures of UDG bound to double-stranded DNA suggest enzyme-DNA, substrate-binding energy from the macromolecular interface is funneled, into catalytic power at the active site. The architecturally stabilized, closing of UDG enforces distortions of the uracil and deoxyribose in the, flipped-out nucleotide substrate that are relieved by glycosylic bond, cleavage in the product complex. This experimentally defined substrate, stereochemistry implies the enzyme alters the orientation of three, orthogonal electron orbitals to favor electron transpositions for, glycosylic bond cleavage. By revealing the coupling of this anomeric, effect to a delocalization of the glycosylic bond electrons into the, uracil aromatic system, this structurally implicated mechanism resolves, apparent paradoxes concerning the transpositions of electrons among, orthogonal orbitals and the retention of catalytic efficiency despite, mutational removal of active-site functional groups. These UDG/DNA, structures and their implied dissociative excision chemistry suggest, biology favors a chemistry for base-excision repair initiation that, optimizes pathway coordination by product binding to avoid the release of, cytotoxic and mutagenic intermediates. Similar excision chemistry may, apply to other biological reaction pathways requiring the coordination of, complex multistep chemical transformations.
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<StructureSection load='1emh' size='340' side='right'caption='[[1emh]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1emh]] 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=1EMH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EMH FirstGlance]. <br>
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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]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P2U:2-DEOXY-PSEUDOURIDINE-5MONOPHOSPHATE'>P2U</scene></td></tr>
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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=1emh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1emh OCA], [https://pdbe.org/1emh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1emh RCSB], [https://www.ebi.ac.uk/pdbsum/1emh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1emh ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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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/em/1emh_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=1emh ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Immunodeficiency with hyper IgM, type 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191525 191525]]
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*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1EMH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EMH OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Uracil-DNA glycosylase-DNA substrate and product structures: conformational strain promotes catalytic efficiency by coupled stereoelectronic effects., Parikh SS, Walcher G, Jones GD, Slupphaug G, Krokan HE, Blackburn GM, Tainer JA, Proc Natl Acad Sci U S A. 2000 May 9;97(10):5083-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10805771 10805771]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Uridine nucleosidase]]
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[[Category: Blackburn GM]]
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[[Category: Blackburn, G.M.]]
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[[Category: Krokan HE]]
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[[Category: Krokan, H.E.]]
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[[Category: Parikh SS]]
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[[Category: Parikh, S.S.]]
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[[Category: Slupphaug G]]
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[[Category: Slupphaug, G.]]
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[[Category: Tainer JA]]
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[[Category: Tainer, J.A.]]
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[[Category: alpha/beta fold]]
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[[Category: protein/dna]]
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[[Category: uracil-dna glycosylase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:44:55 2007''
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Current revision

CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO UNCLEAVED SUBSTRATE-CONTAINING DNA

PDB ID 1emh

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