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| | ==Crystal structure of Aspergillus fumigatus UDP galactopyranose mutase in reduced state== | | ==Crystal structure of Aspergillus fumigatus UDP galactopyranose mutase in reduced state== |
| - | <StructureSection load='3utf' size='340' side='right' caption='[[3utf]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='3utf' size='340' side='right'caption='[[3utf]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3utf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UTF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UTF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3utf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UTF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.25Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ute|3ute]], [[3utg|3utg]], [[3uth|3uth]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glf, glfA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=746128 Aspergillus fumigatus])</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=3utf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3utf OCA], [https://pdbe.org/3utf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3utf RCSB], [https://www.ebi.ac.uk/pdbsum/3utf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3utf 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/UDP-galactopyranose_mutase UDP-galactopyranose mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.9 5.4.99.9] </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=3utf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3utf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3utf RCSB], [http://www.ebi.ac.uk/pdbsum/3utf PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q4W1X2_ASPFM Q4W1X2_ASPFM] |
| - | UDP-galactopyranose mutase (UGM) is a flavoenzyme that catalyzes the conversion of UDP-galactopyranose to UDP-galactofuranose, which is a central reaction in galactofuranose biosynthesis. Galactofuranose has never been found in humans but is an essential building block of the cell wall and extracellular matrix of many bacteria, fungi, and protozoa. The importance of UGM for the viability of many pathogens and its absence in humans makes UGM a potential drug target. Here we report crystal structures and small-angle X-ray scattering data for UGM from the fungus Aspergillus fumigatus, the causative agent of aspergillosis. The structures reveal that Aspergillus UGM has several extra secondary and tertiary structural elements that are not found in bacterial UGMs yet are important for substrate recognition and oligomerization. Small-angle X-ray scattering data show that Aspergillus UGM forms a tetramer in solution, which is unprecedented for UGMs. The binding of UDP or the substrate induces profound conformational changes in the enzyme. Two loops on opposite sides of the active site move toward each other by over 10 A to cover the substrate and create a closed active site. The degree of substrate-induced conformational change exceeds that of bacterial UGMs and is a direct consequence of the unique quaternary structure of Aspergillus UGM. Galactopyranose binds at the re face of the FAD isoalloxazine with the anomeric carbon atom poised for nucleophilic attack by the FAD N5 atom. The structural data provide new insight into substrate recognition and the catalytic mechanism and thus will aid inhibitor design.
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| - | Crystal structures and small-angle X-ray scattering analysis of UDP-galactopyranose mutase from the pathogenic fungus Aspergillus fumigatus.,Dhatwalia R, Singh H, Oppenheimer M, Karr DB, Nix JC, Sobrado P, Tanner JJ J Biol Chem. 2012 Jan 31. PMID:22294687<ref>PMID:22294687</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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| | ==See Also== | | ==See Also== |
| - | *[[UDP-galactopyranose mutase|UDP-galactopyranose mutase]] | + | *[[UDP-galactopyranose mutase 3D structures|UDP-galactopyranose mutase 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Aspergillus fumigatus]] | | [[Category: Aspergillus fumigatus]] |
| - | [[Category: UDP-galactopyranose mutase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dhatwalia, R]] | + | [[Category: Dhatwalia R]] |
| - | [[Category: Singh, H]] | + | [[Category: Singh H]] |
| - | [[Category: Tanner, J J]] | + | [[Category: Tanner JJ]] |
| - | [[Category: Flavin adenine dinucleotide binding]]
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| - | [[Category: Isomerase]]
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| - | [[Category: Mutase]]
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| - | [[Category: Nucleotide binding]]
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