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| ==Crystal structure of Metarhizium anisopliae IDCase in apo form== | | ==Crystal structure of Metarhizium anisopliae IDCase in apo form== |
| <StructureSection load='4hjw' size='340' side='right' caption='[[4hjw]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='4hjw' size='340' side='right'caption='[[4hjw]], [[Resolution|resolution]] 2.60Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4hjw]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Entomophthora_anisopliae Entomophthora anisopliae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HJW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HJW FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4hjw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Metarhizium_anisopliae Metarhizium anisopliae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HJW FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hk5|4hk5]], [[4hk6|4hk6]], [[4hk7|4hk7]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAA_05919 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5530 Entomophthora anisopliae])</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=4hjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hjw OCA], [https://pdbe.org/4hjw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hjw RCSB], [https://www.ebi.ac.uk/pdbsum/4hjw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hjw ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uracil-5-carboxylate_decarboxylase Uracil-5-carboxylate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.66 4.1.1.66] </span></td></tr>
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| <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=4hjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hjw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hjw RCSB], [http://www.ebi.ac.uk/pdbsum/4hjw PDBsum]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/E9F0X0_METRA E9F0X0_METRA] |
| DNA methylation and demethylation regulate many crucial biological processes in mammals and are linked to many diseases. Active DNA demethylation is believed to be catalyzed by TET proteins and a putative DNA decarboxylase that may share some similarities in sequence, structure and catalytic mechanism with isoorotate decarboxylase (IDCase) that catalyzes decarboxylation of 5caU to U in fungi. We report here the structures of wild-type and mutant IDCases from Cordyceps militaris and Metarhizium anisopliae in apo form or in complexes with 5caU, U, and an inhibitor 5-nitro-uracil. IDCases adopt a typical (beta/alpha)8 barrel fold of the amidohydrolase superfamily and function as dimers. A Zn2+ is bound at the active site and coordinated by four strictly conserved residues, one Asp and three His. The substrate is recognized by several strictly conserved residues. The functional roles of the key residues at the active site are validated by mutagenesis and biochemical studies. Based on the structural and biochemical data, we present for the first time a novel catalytic mechanism of decarboxylation for IDCases, which might also apply to other members of the amidohydrolase superfamily. In addition, our biochemical data show that IDCases can catalyze decarboxylation of 5caC to C albeit with weak activity, which is the first in vitro evidence for direct decarboxylation of 5caC to C by an enzyme. These findings are valuable in the identification of potential DNA decarboxylase in mammals.Cell Research advance online publication 6 August 2013; doi:10.1038/cr.2013.107.
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| Crystal structures of isoorotate decarboxylases reveal a novel catalytic mechanism of 5-carboxyl-uracil decarboxylation and shed light on the search for DNA decarboxylase.,Xu S, Li W, Zhu J, Wang R, Li Z, Xu GL, Ding J Cell Res. 2013 Aug 6. doi: 10.1038/cr.2013.107. PMID:23917530<ref>PMID:23917530</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Entomophthora anisopliae]] | | [[Category: Large Structures]] |
| [[Category: Uracil-5-carboxylate decarboxylase]] | | [[Category: Metarhizium anisopliae]] |
| [[Category: Ding, J]] | | [[Category: Ding J]] |
| [[Category: Xu, S]] | | [[Category: Xu S]] |
| [[Category: Zhu, J]] | | [[Category: Zhu J]] |
| [[Category: Decarboxylase]]
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| [[Category: Dna decarboxylation]]
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| [[Category: Idcase]]
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| [[Category: Lyase]]
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| [[Category: Pyrimidine metabolism]]
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| [[Category: Uracil]]
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