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| | ==Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase from Ralstonia eutropha in complexed with acetoacetyl-CoA== | | ==Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase from Ralstonia eutropha in complexed with acetoacetyl-CoA== |
| - | <StructureSection load='4n5m' size='340' side='right' caption='[[4n5m]], [[Resolution|resolution]] 1.34Å' scene=''> | + | <StructureSection load='4n5m' size='340' side='right'caption='[[4n5m]], [[Resolution|resolution]] 1.34Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4n5m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Alcaligenes_eutropha_h16 Alcaligenes eutropha h16]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N5M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N5M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4n5m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cupriavidus_necator_H16 Cupriavidus necator H16]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N5M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAA:ACETOACETYL-COENZYME+A'>CAA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAA:ACETOACETYL-COENZYME+A'>CAA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1q7b|1q7b]], [[3vzp|3vzp]], [[4n5l|4n5l]], [[4n5n|4n5n]]</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=4n5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n5m OCA], [https://pdbe.org/4n5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n5m RCSB], [https://www.ebi.ac.uk/pdbsum/4n5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n5m ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">phbB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=381666 Alcaligenes eutropha H16])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetoacetyl-CoA_reductase Acetoacetyl-CoA reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.36 1.1.1.36] </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=4n5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n5m OCA], [http://pdbe.org/4n5m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n5m RCSB], [http://www.ebi.ac.uk/pdbsum/4n5m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n5m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PHAB_CUPNH PHAB_CUPNH] Catalyzes the chiral reduction of acetoacetyl-CoA to (R)-3-hydroxybutyryl-CoA. Is involved in the biosynthesis of polyhydroxybutyrate (PHB), which is accumulated as an intracellular energy reserve material when cells grow under conditions of nutrient limitation.<ref>PMID:23913421</ref> <ref>PMID:24211201</ref> <ref>PMID:2670935</ref> <ref>PMID:2670936</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: Acetoacetyl-CoA reductase]] | + | [[Category: Cupriavidus necator H16]] |
| - | [[Category: Alcaligenes eutropha h16]] | + | [[Category: Large Structures]] |
| - | [[Category: Kim, J E]] | + | [[Category: Kim J-E]] |
| - | [[Category: Kim, K J]] | + | [[Category: Kim K-J]] |
| - | [[Category: Kim, S]] | + | [[Category: Kim S]] |
| - | [[Category: Alpha/beta structure]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
PHAB_CUPNH Catalyzes the chiral reduction of acetoacetyl-CoA to (R)-3-hydroxybutyryl-CoA. Is involved in the biosynthesis of polyhydroxybutyrate (PHB), which is accumulated as an intracellular energy reserve material when cells grow under conditions of nutrient limitation.[1] [2] [3] [4]
Publication Abstract from PubMed
(R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha H16 (RePhaB) is an enzyme that catalyzes the NADPH-dependent reduction of acetoacetyl-CoA, an intermediate of polyhydroxyalkanoates (PHA) synthetic pathways. Polymeric PHA is used to make bioplastics, implant biomaterials, and biofuels. Here, we report the crystal structures of RePhaB apoenzyme and in complex with either NADP+ or acetoacetyl-CoA, which provide the catalytic mechanism of the protein. RePhaB contains a Rossmann fold and a Clamp domain for binding of NADP+ and acetoacetyl-CoA, respectively. The NADP+-bound form of RePhaB structure reveals that the protein has a unique cofactor binding mode. Interestingly, in the RePhaB structure in complex with acetoacetyl-CoA, the conformation of the Clamp domain, especially the Clamp-lid, undergoes a large structural change about 4.6A leading to formation of the substrate pocket. These structural observations, along with the biochemical experiments, suggest that movement of the Clamp-lid enables the substrate binding and ensures the acetoacetyl moiety is located near to the nicotinamide ring of NADP+.
Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha.,Kim J, Chang JH, Kim EJ, Kim KJ Biochem Biophys Res Commun. 2013 Nov 6. pii: S0006-291X(13)01843-3. doi:, 10.1016/j.bbrc.2013.10.150. PMID:24211201[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Matsumoto K, Tanaka Y, Watanabe T, Motohashi R, Ikeda K, Tobitani K, Yao M, Tanaka I, Taguchi S. Directed evolution and structural analysis of NADPH-dependent acetoacetyl-CoA reductase from Ralstonia eutropha reveals two mutations responsible for enhanced kinetics. Appl Environ Microbiol. 2013 Aug 2. PMID:23913421 doi:10.1128/AEM.01768-13
- ↑ Kim J, Chang JH, Kim EJ, Kim KJ. Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha. Biochem Biophys Res Commun. 2013 Nov 6. pii: S0006-291X(13)01843-3. doi:, 10.1016/j.bbrc.2013.10.150. PMID:24211201 doi:http://dx.doi.org/10.1016/j.bbrc.2013.10.150
- ↑ Peoples OP, Sinskey AJ. Poly-beta-hydroxybutyrate biosynthesis in Alcaligenes eutrophus H16. Characterization of the genes encoding beta-ketothiolase and acetoacetyl-CoA reductase. J Biol Chem. 1989 Sep 15;264(26):15293-7. PMID:2670935
- ↑ Peoples OP, Sinskey AJ. Poly-beta-hydroxybutyrate (PHB) biosynthesis in Alcaligenes eutrophus H16. Identification and characterization of the PHB polymerase gene (phbC). J Biol Chem. 1989 Sep 15;264(26):15298-303. PMID:2670936
- ↑ Kim J, Chang JH, Kim EJ, Kim KJ. Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha. Biochem Biophys Res Commun. 2013 Nov 6. pii: S0006-291X(13)01843-3. doi:, 10.1016/j.bbrc.2013.10.150. PMID:24211201 doi:http://dx.doi.org/10.1016/j.bbrc.2013.10.150
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