4c6c

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{{STRUCTURE_4c6c| PDB=4c6c | SCENE= }}
 
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===Crystal structure of the dihydroorotase domain of human CAD in apo- form obtained recombinantly from HEK293 cells.===
 
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{{ABSTRACT_PUBMED_24332717}}
 
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==Function==
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==Crystal structure of the dihydroorotase domain of human CAD in apo- form obtained recombinantly from HEK293 cells.==
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[[http://www.uniprot.org/uniprot/PYR1_HUMAN PYR1_HUMAN]] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
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<StructureSection load='4c6c' size='340' side='right'caption='[[4c6c]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4c6c]] 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=4C6C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C6C 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]] 1.451&#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=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4c6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c6c OCA], [https://pdbe.org/4c6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c6c RCSB], [https://www.ebi.ac.uk/pdbsum/4c6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c6c ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PYR1_HUMAN PYR1_HUMAN] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Upregulation of CAD, the multifunctional protein that initiates and controls the de novo biosynthesis of pyrimidines in animals, is essential for cell proliferation. Deciphering the architecture and functioning of CAD is of interest for its potential usage as an antitumoral target. However, there is no detailed structural information about CAD other than that it self-assembles into hexamers of approximately 1.5 MDa. Here we report the crystal structure and functional characterization of the dihydroorotase domain of human CAD. Contradicting all assumptions, the structure reveals an active site enclosed by a flexible loop with two Zn2+ ions bridged by a carboxylated lysine and a third Zn coordinating a rare histidinate ion. Site-directed mutagenesis and functional assays prove the involvement of the Zn and flexible loop in catalysis. Comparison with homologous bacterial enzymes supports a reclassification of the DHOase family and provides strong evidence against current models of the architecture of CAD.
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==About this Structure==
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Structure, Functional Characterization, and Evolution of the Dihydroorotase Domain of Human CAD.,Grande-Garcia A, Lallous N, Diaz-Tejada C, Ramon-Maiques S Structure. 2013 Dec 10. pii: S0969-2126(13)00428-0. doi:, 10.1016/j.str.2013.10.016. PMID:24332717<ref>PMID:24332717</ref>
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[[4c6c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C6C OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024332717</ref><references group="xtra"/><references/>
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</div>
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[[Category: Gly-Xaa carboxypeptidase]]
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<div class="pdbe-citations 4c6c" style="background-color:#fffaf0;"></div>
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[[Category: Grande-Garcia, A.]]
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[[Category: Lallous, N.]]
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==See Also==
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[[Category: Ramon-Maiques, S.]]
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*[[CAD protein 3D structures|CAD protein 3D structures]]
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[[Category: Amidohydrolase superfamily]]
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== References ==
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[[Category: De novo pyrimidine biosynthesis]]
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<references/>
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[[Category: Histidinate anion]]
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__TOC__
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[[Category: Hydrolase]]
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</StructureSection>
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[[Category: Metalloenzyme]]
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[[Category: Homo sapiens]]
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[[Category: Zinc binding]]
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[[Category: Large Structures]]
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[[Category: Grande-Garcia A]]
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[[Category: Lallous N]]
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[[Category: Ramon-Maiques S]]

Current revision

Crystal structure of the dihydroorotase domain of human CAD in apo- form obtained recombinantly from HEK293 cells.

PDB ID 4c6c

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