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| | <StructureSection load='6zll' size='340' side='right'caption='[[6zll]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='6zll' size='340' side='right'caption='[[6zll]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6zll]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_cereus_hua2-4 Bacillus cereus hua2-4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZLL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZLL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6zll]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus_HuA2-4 Bacillus cereus HuA2-4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZLL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=UGB:(2S,3R,4S,5R,6R)-6-[[[(2R,3S,4R,5R)-5-(2,4-DIOXOPYRIMIDIN-1-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXY-HYDROXY-PHOSPHORYL]OXY-HYDROXY-PHOSPHORYL]OXY-3,4,5-TRIHYDROXY-OXANE-2-CARBOXYLIC+ACID'>UGB</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]] 1.85Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IG7_05634 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1053203 Bacillus cereus HuA2-4])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=UGB:(2S,3R,4S,5R,6R)-6-[[[(2R,3S,4R,5R)-5-(2,4-DIOXOPYRIMIDIN-1-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXY-HYDROXY-PHOSPHORYL]OXY-HYDROXY-PHOSPHORYL]OXY-3,4,5-TRIHYDROXY-OXANE-2-CARBOXYLIC+ACID'>UGB</scene></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=6zll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zll OCA], [http://pdbe.org/6zll PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zll RCSB], [http://www.ebi.ac.uk/pdbsum/6zll PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zll ProSAT]</span></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=6zll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zll OCA], [https://pdbe.org/6zll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zll RCSB], [https://www.ebi.ac.uk/pdbsum/6zll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zll ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus cereus hua2-4]] | + | [[Category: Bacillus cereus HuA2-4]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Iacovino, L G]] | + | [[Category: Iacovino LG]] |
| - | [[Category: Mattevi, A]] | + | [[Category: Mattevi A]] |
| - | [[Category: Savino, S]] | + | [[Category: Savino S]] |
| - | [[Category: Epimerase]]
| + | |
| - | [[Category: Nad]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Udp-galacturonic acid]]
| + | |
| - | [[Category: Udp-sugar binding protein]]
| + | |
| Structural highlights
Publication Abstract from PubMed
UDP-glucuronic acid is converted to UDP-galacturonic acid en route to a variety of sugar-containing metabolites. This reaction is performed by a NAD(+)-dependent epimerase belonging to the short-chain dehydrogenase/reductase family. We present several high-resolution crystal structures of the UDP-glucuronic acid epimerase from Bacillus cereus The geometry of the substrate-NAD(+) interactions is finely arranged to promote hydride transfer. The exquisite complementarity between glucuronic acid and its binding site is highlighted by the observation that the unligated cavity is occupied by a cluster of ordered waters whose positions overlap the polar groups of the sugar substrate. Co-crystallization experiments led to a structure where substrate- and product-bound enzymes coexist within the same crystal. This equilibrium structure reveals the basis for a "swing & flip" rotation of the pro-chiral 4-keto-hexose-uronic acid intermediate that results from glucuronic acid oxidation, placing the C4' atom in position for receiving a hydride ion on the opposite side of the sugar ring. The product-bound active site is almost identical to that of the substrate-bound structure and satisfies all hydrogen-bonding requirements of the ligand. The structure of the apo-enzyme together with kinetic isotope effect and mutagenesis experiments further outlines a few flexible loops that exist in discrete conformations, imparting structural malleability required for ligand rotation while avoiding leakage of the catalytic intermediate and/or side-reactions. These data highlight the double nature of the enzymatic mechanism: the active site features a high degree of precision in substrate recognition combined with the flexibility required for intermediate rotation.
Crystallographic snapshots of UDP-glucuronic acid 4-epimeraseligand binding, rotation and reduction.,Iacovino LG, Savino S, Borg AJE, Binda C, Nidetzky B, Mattevi A J Biol Chem. 2020 Jul 13. pii: RA120.014692. doi: 10.1074/jbc.RA120.014692. PMID:32661196[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Iacovino LG, Savino S, Borg AJE, Binda C, Nidetzky B, Mattevi A. Crystallographic snapshots of UDP-glucuronic acid 4-epimeraseligand binding, rotation and reduction. J Biol Chem. 2020 Jul 13. pii: RA120.014692. doi: 10.1074/jbc.RA120.014692. PMID:32661196 doi:http://dx.doi.org/10.1074/jbc.RA120.014692
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