6gpl
From Proteopedia
(Difference between revisions)
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==Crystal structure of human GDP-D-mannose 4,6-dehydratase in complex with GDP-4k6d-Man== | ==Crystal structure of human GDP-D-mannose 4,6-dehydratase in complex with GDP-4k6d-Man== | ||
| - | <StructureSection load='6gpl' size='340' side='right' caption='[[6gpl]], [[Resolution|resolution]] 1.76Å' scene=''> | + | <StructureSection load='6gpl' size='340' side='right'caption='[[6gpl]], [[Resolution|resolution]] 1.76Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6gpl]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GPL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GPL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gpl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GPL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GPL FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=F7E:[[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-6-oxidanylidene-1~{H}-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},6~{R})-6-methyl-3,4-bis(oxidanyl)-5-oxidanylidene-oxan-2-yl]+hydrogen+phosphate'>F7E</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=F7E:[[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-6-oxidanylidene-1~{H}-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},6~{R})-6-methyl-3,4-bis(oxidanyl)-5-oxidanylidene-oxan-2-yl]+hydrogen+phosphate'>F7E</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GMDS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=6gpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gpl OCA], [http://pdbe.org/6gpl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gpl RCSB], [http://www.ebi.ac.uk/pdbsum/6gpl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gpl ProSAT]</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=6gpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gpl OCA], [http://pdbe.org/6gpl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gpl RCSB], [http://www.ebi.ac.uk/pdbsum/6gpl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gpl ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/GMDS_HUMAN GMDS_HUMAN]] Conversion of GDP-D-mannose to GDP-4-keto-6-D-deoxymannose. | [[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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6gpl" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: GDP-mannose 4,6-dehydratase]] | [[Category: GDP-mannose 4,6-dehydratase]] | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Arrowsmith, C H]] | [[Category: Arrowsmith, C H]] | ||
[[Category: Bountra, C]] | [[Category: Bountra, C]] | ||
Current revision
Crystal structure of human GDP-D-mannose 4,6-dehydratase in complex with GDP-4k6d-Man
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