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| | ==Crystal Structure of Human DHRS6== | | ==Crystal Structure of Human DHRS6== |
| - | <StructureSection load='2ag5' size='340' side='right' caption='[[2ag5]], [[Resolution|resolution]] 1.84Å' scene=''> | + | <StructureSection load='2ag5' size='340' side='right'caption='[[2ag5]], [[Resolution|resolution]] 1.84Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ag5]] 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=2AG5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AG5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ag5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AG5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </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=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHRS6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHRS6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2ag5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ag5 OCA], [http://pdbe.org/2ag5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ag5 RCSB], [http://www.ebi.ac.uk/pdbsum/2ag5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ag5 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=2ag5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ag5 OCA], [https://pdbe.org/2ag5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ag5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ag5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ag5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BDH2_HUMAN BDH2_HUMAN]] Dehydrogenase that mediates the formation of 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin and associates with LCN2, thereby playing a key role in iron homeostasis and transport. Also acts as a 3-hydroxybutyrate dehydrogenase (By similarity). | + | [[https://www.uniprot.org/uniprot/BDH2_HUMAN BDH2_HUMAN]] Dehydrogenase that mediates the formation of 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin and associates with LCN2, thereby playing a key role in iron homeostasis and transport. Also acts as a 3-hydroxybutyrate dehydrogenase (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Arrowsmith, C]] | | [[Category: Arrowsmith, C]] |
| | [[Category: Delft, F Von]] | | [[Category: Delft, F Von]] |
| Structural highlights
Function
[BDH2_HUMAN] Dehydrogenase that mediates the formation of 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin and associates with LCN2, thereby playing a key role in iron homeostasis and transport. Also acts as a 3-hydroxybutyrate dehydrogenase (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human DHRS6 is a previously uncharacterized member of the short chain dehydrogenases/reductase family and displays significant homologies to bacterial hydroxybutyrate dehydrogenases. Substrate screening reveals sole NAD(+)-dependent conversion of (R)-hydroxybutyrate to acetoacetate with K(m) values of about 10 mm, consistent with plasma levels of circulating ketone bodies in situations of starvation or ketoacidosis. The structure of human DHRS6 was determined at a resolution of 1.8 A in complex with NAD(H) and reveals a tetrameric organization with a short chain dehydrogenases/reductase-typical folding pattern. A highly conserved triad of Arg residues ("triple R" motif consisting of Arg(144), Arg(188), and Arg(205)) was found to bind a sulfate molecule at the active site. Docking analysis of R-beta-hydroxybutyrate into the active site reveals an experimentally consistent model of substrate carboxylate binding and catalytically competent orientation. GFP reporter gene analysis reveals a cytosolic localization upon transfection into mammalian cells. These data establish DHRS6 as a novel, cytosolic type 2 (R)-hydroxybutyrate dehydrogenase, distinct from its well characterized mitochondrial type 1 counterpart. The properties determined for DHRS6 suggest a possible physiological role in cytosolic ketone body utilization, either as a secondary system for energy supply in starvation or to generate precursors for lipid and sterol synthesis.
Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: a novel, cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase.,Guo K, Lukacik P, Papagrigoriou E, Meier M, Lee WH, Adamski J, Oppermann U J Biol Chem. 2006 Apr 14;281(15):10291-7. Epub 2005 Dec 27. PMID:16380372[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Guo K, Lukacik P, Papagrigoriou E, Meier M, Lee WH, Adamski J, Oppermann U. Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: a novel, cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase. J Biol Chem. 2006 Apr 14;281(15):10291-7. Epub 2005 Dec 27. PMID:16380372 doi:10.1074/jbc.M511346200
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