View source for 6q94


==Crystal structure of human GDP-D-mannose 4,6-dehydratase (S156D) in complex with GDP-Man==
<StructureSection load='6q94' size='340' side='right'caption='[[6q94]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6q94]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q94 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q94 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GDD:GUANOSINE-5-DIPHOSPHATE-ALPHA-D-MANNOSE'>GDD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/GDP-mannose_4,6-dehydratase GDP-mannose 4,6-dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.47 4.2.1.47] </span></td></tr>
<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=6q94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q94 OCA], [http://pdbe.org/6q94 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q94 RCSB], [http://www.ebi.ac.uk/pdbsum/6q94 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q94 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/GMDS_HUMAN GMDS_HUMAN]] Conversion of GDP-D-mannose to GDP-4-keto-6-D-deoxymannose. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Biosynthesis of 6-deoxy sugars, including l-fucose, involves a mechanistically complex, enzymatic 4,6-dehydration of hexose nucleotide precursors as the first committed step. Here, we determined pre- and postcatalytic complex structures of the human GDP-mannose 4,6-dehydratase at atomic resolution. These structures together with results of molecular dynamics simulation and biochemical characterization of wildtype and mutant enzymes reveal elusive mechanistic details of water elimination from GDP-mannose C5'' and C6'', coupled to NADP-mediated hydride transfer from C4'' to C6''. We show that concerted acid-base catalysis from only two active-site groups, Tyr179 and Glu157, promotes a syn 1,4-elimination from an enol (not an enolate) intermediate. We also show that the overall multistep catalytic reaction involves the fewest position changes of enzyme and substrate groups and that it proceeds under conserved exploitation of the basic (minimal) catalytic machinery of short-chain dehydrogenase/reductases.

A Parsimonious Mechanism of Sugar Dehydration by Human GDP-Mannose-4,6-dehydratase.,Pfeiffer M, Johansson C, Krojer T, Kavanagh KL, Oppermann U, Nidetzky B ACS Catal. 2019 Apr 5;9(4):2962-2968. doi: 10.1021/acscatal.9b00064. Epub 2019, Mar 1. PMID:30984471<ref>PMID:30984471</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6q94" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: GDP-mannose 4,6-dehydratase]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Delft, F von]]
[[Category: Edwards, A]]
[[Category: Johansson, C]]
[[Category: Krojer, T]]
[[Category: Nidetzky, B]]
[[Category: Oppermann, U]]
[[Category: Pfeiffer, M]]
[[Category: Structural genomic]]
[[Category: Dehydratase]]
[[Category: Fucosylation]]
[[Category: Gdp-mannose 4]]
[[Category: Lyase]]
[[Category: Sgc]]