4c6f: Difference between revisions
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==Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 6.5== | |||
<StructureSection load='4c6f' size='340' side='right' caption='[[4c6f]], [[Resolution|resolution]] 1.26Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4c6f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C6F FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOR:(4S)-2,6-DIOXOHEXAHYDROPYRIMIDINE-4-CARBOXYLIC+ACID'>DOR</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NCD:N-CARBAMOYL-L-ASPARTATE'>NCD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c6b|4c6b]], [[4c6c|4c6c]], [[4c6d|4c6d]], [[4c6e|4c6e]], [[4c6i|4c6i]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroorotase Dihydroorotase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.3 3.5.2.3] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4c6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c6f RCSB], [http://www.ebi.ac.uk/pdbsum/4c6f PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[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). | [[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). | ||
<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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dihydroorotase]] | [[Category: Dihydroorotase]] | ||
[[Category: Grande-Garcia, A | [[Category: Human]] | ||
[[Category: Lallous, N | [[Category: Grande-Garcia, A]] | ||
[[Category: Ramon-Maiques, S | [[Category: Lallous, N]] | ||
[[Category: Ramon-Maiques, S]] | |||
[[Category: Amidohydrolase superfamily]] | [[Category: Amidohydrolase superfamily]] | ||
[[Category: Histidinate anion]] | [[Category: Histidinate anion]] | ||
Revision as of 17:29, 24 December 2014
Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 6.5Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 6.5
Structural highlights
Function[PYR1_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. References
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