2foz

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(New page: 200px<br /> <applet load="2foz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2foz, resolution 1.60&Aring;" /> '''human ADP-ribosylhy...)
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[[Image:2foz.gif|left|200px]]<br />
 
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<applet load="2foz" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2foz, resolution 1.60&Aring;" />
 
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'''human ADP-ribosylhydrolase 3'''<br />
 
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==Overview==
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==human ADP-ribosylhydrolase 3==
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Posttranslational modifications are used by cells from all kingdoms of, life to control enzymatic activity and to regulate protein function. For, many cellular processes, including DNA repair, spindle function, and, apoptosis, reversible mono- and polyADP-ribosylation constitutes a very, important regulatory mechanism. Moreover, many pathogenic bacteria secrete, toxins which ADP-ribosylate human proteins, causing diseases such as, whooping cough, cholera, and diphtheria. Whereas the 3D structures of, numerous ADP-ribosylating toxins and related mammalian enzymes have been, elucidated, virtually nothing is known about the structure of protein, de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human, ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3, constitutes the archetype of an all-alpha-helical protein fold and, provides insights into the reversibility of protein ADP-ribosylation. Two, magnesium ions flanked by highly conserved amino acids pinpoint the, active-site crevice. Recombinant hARH3 binds free ADP-ribose with, micromolar affinity and efficiently de-ADP-ribosylates poly- but not, monoADP-ribosylated proteins. Docking experiments indicate a possible, binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our, results underscore the importance of endogenous ADP-ribosylation cycles, and provide a basis for structure-based design of ADP-ribosylhydrolase, inhibitors.
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<StructureSection load='2foz' size='340' side='right'caption='[[2foz]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2foz]] is a 1 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=2FOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FOZ FirstGlance]. <br>
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2FOZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FOZ OCA].
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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]] 1.6&#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=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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==Reference==
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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=2foz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2foz OCA], [https://pdbe.org/2foz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2foz RCSB], [https://www.ebi.ac.uk/pdbsum/2foz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2foz ProSAT]</span></td></tr>
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The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation., Mueller-Dieckmann C, Kernstock S, Lisurek M, von Kries JP, Haag F, Weiss MS, Koch-Nolte F, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15026-31. Epub 2006 Oct 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17015823 17015823]
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ADPRS_HUMAN ADPRS_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/ADPRS_HUMAN ADPRS_HUMAN] ADP-ribose glycohydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:30045870, PubMed:29907568, PubMed:30401461, PubMed:33186521). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885).<ref>PMID:16278211</ref> <ref>PMID:17075046</ref> <ref>PMID:21498885</ref> <ref>PMID:22433848</ref> <ref>PMID:28650317</ref> <ref>PMID:29234005</ref> <ref>PMID:29480802</ref> <ref>PMID:29907568</ref> <ref>PMID:30045870</ref> <ref>PMID:30401461</ref> <ref>PMID:33186521</ref>
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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/fo/2foz_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=2foz ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[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: Koch-Nolte, F.]]
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[[Category: Koch-Nolte F]]
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[[Category: Mueller-Dieckmann, C.]]
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[[Category: Mueller-Dieckmann C]]
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[[Category: Weiss, M.S.]]
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[[Category: Weiss MS]]
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[[Category: MG]]
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[[Category: all alpha-helical]]
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[[Category: metal binding]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:08:59 2007''
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Current revision

human ADP-ribosylhydrolase 3

PDB ID 2foz

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