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| | <StructureSection load='5i34' size='340' side='right'caption='[[5i34]], [[Resolution|resolution]] 1.53Å' scene=''> | | <StructureSection load='5i34' size='340' side='right'caption='[[5i34]], [[Resolution|resolution]] 1.53Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5i34]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Crynh Crynh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I34 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I34 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5i34]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_H99 Cryptococcus neoformans var. grubii H99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I34 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I34 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</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]] 1.53Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5i33|5i33]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNAG_02858 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=235443 CRYNH])</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=5i34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i34 OCA], [https://pdbe.org/5i34 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i34 RCSB], [https://www.ebi.ac.uk/pdbsum/5i34 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i34 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/Adenylosuccinate_synthase Adenylosuccinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.4 6.3.4.4] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5i34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i34 OCA], [http://pdbe.org/5i34 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i34 RCSB], [http://www.ebi.ac.uk/pdbsum/5i34 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i34 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/J9VI09_CRYNH J9VI09_CRYNH]] Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first commited step in the biosynthesis of AMP from IMP.[HAMAP-Rule:MF_03125] Plays an important role in the de novo pathway of purine nucleotide biosynthesis.[RuleBase:RU000520] | + | [https://www.uniprot.org/uniprot/J9VI09_CRYNH J9VI09_CRYNH] Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first commited step in the biosynthesis of AMP from IMP.[HAMAP-Rule:MF_03125] Plays an important role in the de novo pathway of purine nucleotide biosynthesis.[RuleBase:RU000520] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenylosuccinate synthase]] | + | [[Category: Cryptococcus neoformans var. grubii H99]] |
| - | [[Category: Crynh]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Blundell, R D]] | + | [[Category: Blundell RD]] |
| - | [[Category: Ericsson, D]] | + | [[Category: Ericsson D]] |
| - | [[Category: Fraser, J A]] | + | [[Category: Fraser JA]] |
| - | [[Category: Kobe, B]] | + | [[Category: Kobe B]] |
| - | [[Category: Williams, S J]] | + | [[Category: Williams SJ]] |
| - | [[Category: Adenylosuccinate synthetase]]
| + | |
| - | [[Category: Dimer]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Purine metabolism]]
| + | |
| Structural highlights
Function
J9VI09_CRYNH Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first commited step in the biosynthesis of AMP from IMP.[HAMAP-Rule:MF_03125] Plays an important role in the de novo pathway of purine nucleotide biosynthesis.[RuleBase:RU000520]
Publication Abstract from PubMed
Opportunistic fungal pathogens such as Cryptococcus neoformans are a growing cause of morbidity and mortality among immunocompromised populations worldwide. To address the current paucity of antifungal therapeutic agents, further research into fungal-specific drug targets is required. Adenylosuccinate synthetase (AdSS) is a crucial enzyme in the adeosine triphosphate (ATP) biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. We have investigated the potential of this enzyme as an antifungal drug target, finding that loss of function results in adenine auxotrophy in C. neoformans, as well as complete loss of virulence in a murine model. Cryptococcal AdSS was expressed and purified in Escherichia coli and the enzyme's crystal structure determined, the first example of a structure of this enzyme from fungi. Together with enzyme kinetic studies, this structural information enabled comparison of the fungal enzyme with the human orthologue and revealed species-specific differences potentially exploitable via rational drug design. These results validate AdSS as a promising antifungal drug target and lay a foundation for future in silico and in vitro screens for novel antifungal compounds.
Disruption of de Novo Adenosine Triphosphate (ATP) Biosynthesis Abolishes Virulence in Cryptococcus neoformans.,Blundell RD, Williams SJ, Arras SD, Chitty JL, Blake KL, Ericsson DJ, Tibrewal N, Rohr J, Koh YQ, Kappler U, Robertson AA, Butler MS, Cooper MA, Kobe B, Fraser JA ACS Infect Dis. 2016 Sep 9;2(9):651-663. Epub 2016 Aug 17. PMID:27759389[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Blundell RD, Williams SJ, Arras SD, Chitty JL, Blake KL, Ericsson DJ, Tibrewal N, Rohr J, Koh YQ, Kappler U, Robertson AA, Butler MS, Cooper MA, Kobe B, Fraser JA. Disruption of de Novo Adenosine Triphosphate (ATP) Biosynthesis Abolishes Virulence in Cryptococcus neoformans. ACS Infect Dis. 2016 Sep 9;2(9):651-663. Epub 2016 Aug 17. PMID:27759389 doi:http://dx.doi.org/10.1021/acsinfecdis.6b00121
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