6zlk
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==Equilibrium Structure of UDP-Glucuronic acid 4-epimerase from Bacillus cereus in complex with UDP-Glucuronic acid/UDP-Galacturonic acid and NAD== | ==Equilibrium Structure of UDP-Glucuronic acid 4-epimerase from Bacillus cereus in complex with UDP-Glucuronic acid/UDP-Galacturonic acid and NAD== | ||
| - | <StructureSection load='6zlk' size='340' side='right'caption='[[6zlk]]' scene=''> | + | <StructureSection load='6zlk' size='340' side='right'caption='[[6zlk]], [[Resolution|resolution]] 1.50Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZLK OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6zlk]] 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=6ZLK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZLK FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</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=UGA:URIDINE-5-DIPHOSPHATE-GLUCURONIC+ACID'>UGA</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'>[https://proteopedia.org/fgij/fg.htm?mol=6zlk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zlk OCA], [https://pdbe.org/6zlk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zlk RCSB], [https://www.ebi.ac.uk/pdbsum/6zlk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zlk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:32661196</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6zlk" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus cereus HuA2-4]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Iacovino LG]] | [[Category: Iacovino LG]] | ||
[[Category: Mattevi A]] | [[Category: Mattevi A]] | ||
Current revision
Equilibrium Structure of UDP-Glucuronic acid 4-epimerase from Bacillus cereus in complex with UDP-Glucuronic acid/UDP-Galacturonic acid and NAD
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