4c6d: Difference between revisions
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==Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 6.0== | |||
<StructureSection load='4c6d' size='340' side='right'caption='[[4c6d]], [[Resolution|resolution]] 1.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4c6d]] 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=4C6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C6D FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.298Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOR:(4S)-2,6-DIOXOHEXAHYDROPYRIMIDINE-4-CARBOXYLIC+ACID'>DOR</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=NCD:N-CARBAMOYL-L-ASPARTATE'>NCD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4c6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c6d OCA], [https://pdbe.org/4c6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c6d RCSB], [https://www.ebi.ac.uk/pdbsum/4c6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c6d ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4c6d" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[CAD protein 3D structures|CAD protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Grande-Garcia A]] | |||
[[Category: Lallous N]] | |||
[[Category: Ramon-Maiques S]] | |||
Latest revision as of 15:04, 20 December 2023
Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 6.0Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 6.0
Structural highlights
FunctionPYR1_HUMAN This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). Publication Abstract from PubMedUpregulation 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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