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| | + | '''Unreleased structure''' |
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| - | ==NADase from Aspergillus fumigatus with replaced C-terminus from Neurospora crassa==
| + | The entry 8pms is ON HOLD until Paper Publication |
| - | <StructureSection load='8pms' size='340' side='right'caption='[[8pms]], [[Resolution|resolution]] 2.40Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[8pms]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PMS 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]] 2.4Å</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=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8pms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pms OCA], [https://pdbe.org/8pms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pms RCSB], [https://www.ebi.ac.uk/pdbsum/8pms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pms ProSAT]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [https://www.uniprot.org/uniprot/NADA_ASPFU NADA_ASPFU] Conidial surface nicotinamide adenine dinucleotide glycohydrolase that cleave NAD(+) and NADP(+) but not their reduced counterparts, NADH and NADPH (PubMed:33712585). Lacks both ADP-ribosyl cyclase and base exchange activity and does not mediate synthesis of calcium messengers cADPR or NAADP (PubMed:33712585). Plays a role in pathogenicity by depleting the host's NAD(+) pool (PubMed:33712585).<ref>PMID:33712585</ref>
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Nicotinamide adenine dinucleotide (NAD) is an essential molecule in all kingdoms of life, mediating energy metabolism and cellular signaling. Recently, a new class of highly active fungal surface NADases was discovered. The enzyme from the opportunistic human pathogen Aspergillus fumigatus was thoroughly characterized. It harbors a catalytic domain that resembles that of the tuberculosis necrotizing toxin from Mycobacterium tuberculosis, which efficiently cleaves NAD(+) to nicotinamide and ADP-ribose, thereby depleting the dinucleotide pool. Of note, the A. fumigatus NADase has an additional Ca(2+)-binding motif at the C-terminus of the protein. Despite the presence of NADases in several fungal divisions, the Ca(2+)-binding motif is uniquely found in the Eurotiales order, which contains species that have immense health and economic impacts on humans. To identify the potential roles of the metal ion-binding site in catalysis or protein stability, we generated and characterized A. fumigatus NADase variants lacking the ability to bind calcium. X-ray crystallographic analyses revealed that the mutation causes a drastic and dynamic structural rearrangement of the homodimer, resulting in decreased thermal stability. Even though the calcium-binding site is at a long distance from the catalytic center, the structural reorganization upon the loss of calcium binding allosterically alters the active site, thereby negatively affecting NAD-glycohydrolase activity. Together, these findings reveal that this unique calcium-binding site affects the protein fold, stabilizing the dimeric structure, but also mediates long-range effects resulting in an increased catalytic rate.
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| - | Novel Calcium-Binding Motif Stabilizes and Increases the Activity of Aspergillus fumigatus Ecto-NADase.,Ferrario E, Kallio JP, Stromland O, Ziegler M Biochemistry. 2023 Nov 7. doi: 10.1021/acs.biochem.3c00360. PMID:37934975<ref>PMID:37934975</ref>
| + | Authors: |
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | Description: |
| - | </div>
| + | [[Category: Unreleased Structures]] |
| - | <div class="pdbe-citations 8pms" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Aspergillus fumigatus Af293]] | + | |
| - | [[Category: Large Structures]]
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| - | [[Category: Ferrario E]]
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| - | [[Category: Kallio JP]]
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| - | [[Category: Stromland O]]
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| - | [[Category: Ziegler M]]
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