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| | ==Crystal structure of the dehydrogenase/reductase SDR family member 4 (DHRS4) from Caenorhabditis elegans== | | ==Crystal structure of the dehydrogenase/reductase SDR family member 4 (DHRS4) from Caenorhabditis elegans== |
| - | <StructureSection load='5oji' size='340' side='right' caption='[[5oji]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='5oji' size='340' side='right'caption='[[5oji]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oji]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OJI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OJI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oji]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OJI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ISN:ISATIN'>ISN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dhrs-4, F54F3.4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ISN:ISATIN'>ISN</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/Carbonyl_reductase_(NADPH) Carbonyl reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.184 1.1.1.184] </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=5oji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oji OCA], [https://pdbe.org/5oji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oji RCSB], [https://www.ebi.ac.uk/pdbsum/5oji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oji 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=5oji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oji OCA], [http://pdbe.org/5oji PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oji RCSB], [http://www.ebi.ac.uk/pdbsum/5oji PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oji ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DHRS4_CAEEL DHRS4_CAEEL]] Catalyzes the reduction of isatin, 4-oxonon-2-enal, 9,10-phenanthrenequinone, menadione, 2,3-hexaenadione, 3,4-hexanedione and 2,3-heptanedione.<ref>PMID:21300042</ref> | + | [https://www.uniprot.org/uniprot/DHRS4_CAEEL DHRS4_CAEEL] Catalyzes the reduction of isatin, 4-oxonon-2-enal, 9,10-phenanthrenequinone, menadione, 2,3-hexaenadione, 3,4-hexanedione and 2,3-heptanedione.<ref>PMID:21300042</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| - | [[Category: Ebert, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Faust, A]] | + | [[Category: Ebert B]] |
| - | [[Category: Kisiela, M]] | + | [[Category: Faust A]] |
| - | [[Category: Maser, E]] | + | [[Category: Kisiela M]] |
| - | [[Category: Scheidig, A J]] | + | [[Category: Maser E]] |
| - | [[Category: Dehydrogenase sdr biotransformation]]
| + | [[Category: Scheidig AJ]] |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
DHRS4_CAEEL Catalyzes the reduction of isatin, 4-oxonon-2-enal, 9,10-phenanthrenequinone, menadione, 2,3-hexaenadione, 3,4-hexanedione and 2,3-heptanedione.[1]
Publication Abstract from PubMed
The human dehydrogenase/reductase SDR family member 4 (DHRS4) is a tetrameric protein that is involved in the metabolism of several aromatic carbonyl compounds, steroids and bile acids. The only invertebrate DHRS4 that has been characterized to date is that from the model organism Caenorhabditis elegans. We have previously cloned and initially characterized this protein that was recently annotated as DHRS4_CAEEL in the UniProtKB database. Crystallization and X-ray diffraction studies of the full-length DHRS4_CAEEL protein in complex with diacetyl revealed its tetrameric structure and showed that two subunits are connected via an intermolecular disulfide bridge that is formed by N-terminal cysteine residues (Cys5) of each protein chain, which increases the enzymatic activity. A more detailed biochemical and catalytic characterization shows that DHRS4_CAEEL shares some properties with human DHRS4 such as relatively low substrate affinities with aliphatic alpha-diketones and a preference for aromatic dicarbonyls such as isatin, with a 30-fold lower Km value compared to the human enzyme. Moreover, DHRS4_CAEEL is active with aliphatic aldehydes (e.g., hexanal), while human DHRS4 is not. Dehydrogenase activity with alcohols was only observed with aromatic alcohols. Protein thermal shift assay revealed a stabilizing effect of phosphate buffer that was accompanied by an increase in catalytic activity of more that 2-fold. The study of DHRS4 homologs in simple lineages such as C. elegans may contribute to our understanding of the original function of this protein that has been shaped by evolutionary processes in the course of the development from invertebrates to higher mammalian species. This article is protected by copyright. All rights reserved.
Crystal structure and catalytic characterization of the dehydrogenase/reductase SDR family member 4 (DHRS4) from Caenorhabditis elegans.,Kisiela M, Faust A, Ebert B, Maser E, Scheidig AJ FEBS J. 2017 Nov 19. doi: 10.1111/febs.14337. PMID:29151266[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kisiela M, El-Hawari Y, Martin HJ, Maser E. Bioinformatic and biochemical characterization of DCXR and DHRS2/4 from Caenorhabditis elegans. Chem Biol Interact. 2011 May 30;191(1-3):75-82. doi: 10.1016/j.cbi.2011.01.034., Epub 2011 Feb 15. PMID:21300042 doi:http://dx.doi.org/10.1016/j.cbi.2011.01.034
- ↑ Kisiela M, Faust A, Ebert B, Maser E, Scheidig AJ. Crystal structure and catalytic characterization of the dehydrogenase/reductase SDR family member 4 (DHRS4) from Caenorhabditis elegans. FEBS J. 2017 Nov 19. doi: 10.1111/febs.14337. PMID:29151266 doi:http://dx.doi.org/10.1111/febs.14337
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