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| - | | + | #REDIRECT [[5vwu]] This PDB entry is obsolete and replaced by 5vwu |
| - | ==Crystal structure of oxidized Aspergillus fumigatus UDP-galactopyranose mutase complexed with NADH==
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| - | <StructureSection load='4gdd' size='340' side='right' caption='[[4gdd]], [[Resolution|resolution]] 2.75Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[4gdd]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GDD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GDD FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3utf|3utf]], [[3utg|3utg]], [[3uth|3uth]], [[4gdc|4gdc]], [[4gde|4gde]]</td></tr>
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| - | <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=4gdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gdd OCA], [http://pdbe.org/4gdd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gdd RCSB], [http://www.ebi.ac.uk/pdbsum/4gdd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gdd ProSAT]</span></td></tr>
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| - | </table>
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | UDP-galactopyranose mutase (UGM) plays an essential role in galactofuranose biosynthesis in microorganisms by catalyzing the conversion of UDP-galactopyranose to UDP-galactofuranose. The enzyme has gained attention recently as a promising target for the design of new antifungal, antitrypanosomal, and antileishmanial agents. Here we report the first crystal structure of UGM complexed with its redox partner NAD(P)H. Kinetic protein crystallography was used to obtain structures of oxidized Aspergillus fumigatus UGM (AfUGM) complexed with NADPH and NADH, as well as reduced AfUGM after dissociation of NADP+. NAD(P)H binds with the nicotinamide near the FAD isoalloxazine and the ADP moiety extending toward the mobile 200s active site flap. The nicotinamide riboside binding site overlaps that of the substrate galactopyranose moiety, thus NADPH and substrate binding are mutually exclusive. On the other hand, the pockets for the adenine of NADPH and uracil of the substrate are distinct and separated by only 6 A, which raises the possibility of designing novel inhibitors that bind both sites. All twelve residues that contact NADP(H) are conserved among eukaryotic UGMs. Residues that form the AMP pocket are absent in bacterial UGMs, which suggests that eukaryotic and bacterial UGMs have different NADP(H) binding sites. The structures address the longstanding question of how UGM binds NAD(P)H and provide new opportunities for drug discovery.
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| - | Identification of the NAD(P)H Binding Site of Eukaryotic UDP-Galactopyranose Mutase.,Dhatwalia R, Singh H, Solano LM, Oppenheimer M, Robinson RM, Ellerbrock JF, Sobrado P, Tanner JJ J Am Chem Soc. 2012 Oct 4. PMID:23036087<ref>PMID:23036087</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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| - | <div class="pdbe-citations 4gdd" style="background-color:#fffaf0;"></div>
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| - | ==See Also==
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| - | *[[UDP-galactopyranose mutase|UDP-galactopyranose mutase]]
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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: UDP-galactopyranose mutase]]
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| - | [[Category: Dhatwalia, R D]]
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| - | [[Category: Singh, H]]
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| - | [[Category: Tanner, J J]]
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| - | [[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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