1pkh

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[[Image:1pkh.gif|left|200px]]<br /><applet load="1pkh" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1pkh, resolution 1.42&Aring;" />
 
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'''STRUCTURAL BASIS FOR RECOGNITION AND CATALYSIS BY THE BIFUNCTIONAL DCTP DEAMINASE AND DUTPASE FROM METHANOCOCCUS JANNASCHII'''<br />
 
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==Overview==
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==STRUCTURAL BASIS FOR RECOGNITION AND CATALYSIS BY THE BIFUNCTIONAL DCTP DEAMINASE AND DUTPASE FROM METHANOCOCCUS JANNASCHII==
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Potentially mutagenic uracil-containing nucleotide intermediates are generated by deamination of dCTP, either spontaneously or enzymatically as the first step in the conversion of dCTP to dTTP. dUTPases convert dUTP to dUMP, thus avoiding the misincorporation of dUTP into DNA and creating the substrate for the next enzyme in the dTTP synthetic pathway, thymidylate synthase. Although dCTP deaminase and dUTPase activities are usually found in separate but homologous enzymes, the hyperthermophile Methanococcus jannaschii has an enzyme, DCD-DUT, that harbors both dCTP deaminase and dUTP pyrophosphatase activities. DCD-DUT has highest activity on dCTP, followed by dUTP, and dTTP inhibits both the deaminase and pyrophosphatase activities. To help clarify structure-function relationships for DCD-DUT, we have determined the crystal structure of the wild-type DCD-DUT protein in its apo form to 1.42A and structures of DCD-DUT in complex with dCTP and dUTP to resolutions of 1.77A and 2.10A, respectively. To gain insights into substrate interactions, we complemented analyses of the experimentally defined weak density for nucleotides with automated docking experiments using dCTP, dUTP, and dTTP. DCD-DUT is a hexamer, unlike the homologous dUTPases, and its subunits contain several insertions and substitutions different from the dUTPase beta barrel core that likely contribute to dCTP specificity and deamination. These first structures of a dCTP deaminase reveal a probable role for an unstructured C-terminal region different from that of the dUTPases and possible mechanisms for both bifunctional enzyme activity and feedback inhibition by dTTP.
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<StructureSection load='1pkh' size='340' side='right'caption='[[1pkh]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1pkh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PKH 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]] 1.42&#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=EDO:1,2-ETHANEDIOL'>EDO</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=1pkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pkh OCA], [https://pdbe.org/1pkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pkh RCSB], [https://www.ebi.ac.uk/pdbsum/1pkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pkh ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DCDB_METJA DCDB_METJA] Bifunctional enzyme that catalyzes both the deamination of dCTP to dUTP and the hydrolysis of dUTP to dUMP without releasing the toxic dUTP intermediate. It also acts as a dUTP diphosphatase with a lower affinity for dUTP than for dCTP.<ref>PMID:12538648</ref> <ref>PMID:12670946</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/pk/1pkh_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=1pkh ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1PKH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PKH OCA].
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*[[Deaminase 3D structures|Deaminase 3D structures]]
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== References ==
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==Reference==
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<references/>
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Structural basis for recognition and catalysis by the bifunctional dCTP deaminase and dUTPase from Methanococcus jannaschii., Huffman JL, Li H, White RH, Tainer JA, J Mol Biol. 2003 Aug 22;331(4):885-96. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12909016 12909016]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Methanocaldococcus jannaschii]]
[[Category: Methanocaldococcus jannaschii]]
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[[Category: Single protein]]
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[[Category: Huffman JL]]
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[[Category: Huffman, J L.]]
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[[Category: Li H]]
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[[Category: Li, H.]]
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[[Category: Tainer JA]]
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[[Category: Tainer, J A.]]
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[[Category: White RH]]
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[[Category: White, R H.]]
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[[Category: EDO]]
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[[Category: dcd-dut]]
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[[Category: dctp]]
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[[Category: dctp deaminase]]
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[[Category: dutp]]
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[[Category: dutpase]]
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[[Category: mj0430]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:29:47 2008''
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Current revision

STRUCTURAL BASIS FOR RECOGNITION AND CATALYSIS BY THE BIFUNCTIONAL DCTP DEAMINASE AND DUTPASE FROM METHANOCOCCUS JANNASCHII

PDB ID 1pkh

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