View source for 6zll


==Crystal Structure of UDP-Glucuronic acid 4-epimerase from Bacillus cereus in complex with UDP-Galacturonic acid and NAD==
<StructureSection load='6zll' size='340' side='right'caption='[[6zll]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</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'>[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>
<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 &amp; 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6zll" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Bacillus cereus HuA2-4]]
[[Category: Large Structures]]
[[Category: Iacovino LG]]
[[Category: Mattevi A]]
[[Category: Savino S]]