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| | <StructureSection load='5dx9' size='340' side='right'caption='[[5dx9]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='5dx9' size='340' side='right'caption='[[5dx9]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dx9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_32045 Atcc 32045]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DX9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DX9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dx9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DX9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T6P:TREHALOSE-6-PHOSPHATE'>T6P</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]] 2.15Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=G6P:ALPHA-D-GLUCOSE-6-PHOSPHATE'>G6P</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PRD_900039:trehalose-6-phosphate'>PRD_900039</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dxi|5dxi]], [[5dxf|5dxf]], [[5dxl|5dxl]], [[5dxn|5dxn]], [[5dxo|5dxo]]</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=5dx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dx9 OCA], [https://pdbe.org/5dx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dx9 RCSB], [https://www.ebi.ac.uk/pdbsum/5dx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dx9 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPS2, CNAG_03765 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5207 ATCC 32045])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha,alpha-trehalose-phosphate_synthase_(UDP-forming) Alpha,alpha-trehalose-phosphate synthase (UDP-forming)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.15 2.4.1.15] </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=5dx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dx9 OCA], [http://pdbe.org/5dx9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dx9 RCSB], [http://www.ebi.ac.uk/pdbsum/5dx9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dx9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q059G6_CRYNH Q059G6_CRYNH] |
| | <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: Atcc 32045]] | + | [[Category: Cryptococcus neoformans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brennan, R G]] | + | [[Category: Brennan RG]] |
| - | [[Category: Miao, Y]] | + | [[Category: Miao Y]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| - | [[Category: Trehalose-6-phosphate]]
| + | |
| Structural highlights
5dx9 is a 1 chain structure with sequence from Cryptococcus neoformans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.15Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q059G6_CRYNH
Publication Abstract from PubMed
Trehalose is a disaccharide essential for the survival and virulence of pathogenic fungi. The biosynthesis of trehalose requires trehalose-6-phosphate synthase, Tps1, and trehalose-6-phosphate phosphatase, Tps2. Here, we report the structures of the N-terminal domain of Tps2 (Tps2NTD) from Candida albicans, a transition-state complex of the Tps2 C-terminal trehalose-6-phosphate phosphatase domain (Tps2PD) bound to BeF3 and trehalose, and catalytically dead Tps2PD(D24N) from Cryptococcus neoformans bound to trehalose-6-phosphate (T6P). The Tps2NTD closely resembles the structure of Tps1 but lacks any catalytic activity. The Tps2PD-BeF3-trehalose and Tps2PD(D24N)-T6P complex structures reveal a "closed" conformation that is effected by extensive interactions between each trehalose hydroxyl group and residues of the cap and core domains of the protein, thereby providing exquisite substrate specificity. Disruption of any of the direct substrate-protein residue interactions leads to significant or complete loss of phosphatase activity. Notably, the Tps2PD-BeF3-trehalose complex structure captures an aspartyl-BeF3 covalent adduct, which closely mimics the proposed aspartyl-phosphate intermediate of the phosphatase catalytic cycle. Structures of substrate-free Tps2PD reveal an "open" conformation whereby the cap and core domains separate and visualize the striking conformational changes effected by substrate binding and product release and the role of two hinge regions centered at approximately residues 102-103 and 184-188. Significantly, tps2Delta, tps2NTDDelta, and tps2D705N strains are unable to grow at elevated temperatures. Combined, these studies provide a deeper understanding of the substrate recognition and catalytic mechanism of Tps2 and provide a structural basis for the future design of novel antifungal compounds against a target found in three major fungal pathogens.
Structures of trehalose-6-phosphate phosphatase from pathogenic fungi reveal the mechanisms of substrate recognition and catalysis.,Miao Y, Tenor JL, Toffaletti DL, Washington EJ, Liu J, Shadrick WR, Schumacher MA, Lee RE, Perfect JR, Brennan RG Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7148-53. doi:, 10.1073/pnas.1601774113. Epub 2016 Jun 15. PMID:27307435[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miao Y, Tenor JL, Toffaletti DL, Washington EJ, Liu J, Shadrick WR, Schumacher MA, Lee RE, Perfect JR, Brennan RG. Structures of trehalose-6-phosphate phosphatase from pathogenic fungi reveal the mechanisms of substrate recognition and catalysis. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7148-53. doi:, 10.1073/pnas.1601774113. Epub 2016 Jun 15. PMID:27307435 doi:http://dx.doi.org/10.1073/pnas.1601774113
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