Reaction participants Show >> << Hide
- Name help_outline a (3R)-3-hydroxyacyl-CoA Identifier CHEBI:57319 Charge -4 Formula C24H35N7O18P3SR SMILEShelp_outline CC(C)(COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@H](O)[*] 2D coordinates Mol file for the small molecule Search links Involved in 128 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADP+ Identifier CHEBI:58349 Charge -3 Formula C21H25N7O17P3 InChIKeyhelp_outline XJLXINKUBYWONI-NNYOXOHSSA-K SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,285 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline a 3-oxoacyl-CoA Identifier CHEBI:90726 Charge -4 Formula C24H33N7O18P3SR SMILEShelp_outline [C@@H]1(N2C3=C(C(=NC=N3)N)N=C2)O[C@H](COP(OP(OCC([C@H](C(NCCC(NCCSC(=O)CC(=O)*)=O)=O)O)(C)C)(=O)[O-])(=O)[O-])[C@H]([C@H]1O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 180 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADPH Identifier CHEBI:57783 (Beilstein: 10411862) help_outline Charge -4 Formula C21H26N7O17P3 InChIKeyhelp_outline ACFIXJIJDZMPPO-NNYOXOHSSA-J SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,279 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:22256 | RHEA:22257 | RHEA:22258 | RHEA:22259 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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EC numbers help_outline | ||||
Gene Ontology help_outline | ||||
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MetaCyc help_outline |
Related reactions help_outline
Specific form(s) of this reaction
- RHEA:48683
- RHEA:45851
- RHEA:45847
- RHEA:45799
- RHEA:39638
- RHEA:39626
- RHEA:39614
- RHEA:39602
- RHEA:39590
- RHEA:39578
- RHEA:39558
- RHEA:39546
- RHEA:39534
- RHEA:39522
- RHEA:39510
- RHEA:39498
- RHEA:39486
- RHEA:39474
- RHEA:39462
- RHEA:39450
- RHEA:39438
- RHEA:39422
- RHEA:39410
- RHEA:39398
- RHEA:39386
- RHEA:39374
- RHEA:39362
- RHEA:39342
- RHEA:39338
- RHEA:39326
- RHEA:39314
- RHEA:39302
- RHEA:39270
- RHEA:39258
- RHEA:39246
- RHEA:39234
- RHEA:39222
- RHEA:39210
- RHEA:39198
- RHEA:39186
- RHEA:39174
- RHEA:39166
- RHEA:39154
Publications
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Binary structure of the two-domain (3R)-hydroxyacyl-CoA dehydrogenase from rat peroxisomal multifunctional enzyme type 2 at 2.38 A resolution.
Haapalainen A.M., Koski M.K., Qin Y.-M., Hiltunen J.K., Glumoff T.
The crystal structure of (3R)-hydroxyacyl-CoA dehydrogenase of rat peroxisomal multifunctional enzyme type 2 (MFE-2) was solved at 2.38 A resolution. The catalytic entity reveals an alpha/beta short chain alcohol dehydrogenase/reductase (SDR) fold and the conformation of the bound nicotinamide ade ... >> More
The crystal structure of (3R)-hydroxyacyl-CoA dehydrogenase of rat peroxisomal multifunctional enzyme type 2 (MFE-2) was solved at 2.38 A resolution. The catalytic entity reveals an alpha/beta short chain alcohol dehydrogenase/reductase (SDR) fold and the conformation of the bound nicotinamide adenine dinucleotide (NAD(+)) found in other SDR enzymes. Of great interest is the separate COOH-terminal domain, which is not seen in other SDR structures. This domain completes the active site cavity of the neighboring monomer and extends dimeric interactions. Peroxisomal diseases that arise because of point mutations in the dehydrogenase-coding region of the MFE-2 gene can be mapped to changes in amino acids involved in NAD(+) binding and protein dimerization. << Less
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Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha.
Kim J., Chang J.H., Kim E.J., Kim K.J.
(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 bio ... >> More
(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 4.6 Å 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(+). << Less
Biochem. Biophys. Res. Commun. 443:783-788(2014) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Directed evolution and structural analysis of NADPH-dependent acetoacetyl coenzyme A (acetoacetyl-CoA) reductase from Ralstonia eutropha reveals two mutations responsible for enhanced kinetics.
Matsumoto K., Tanaka Y., Watanabe T., Motohashi R., Ikeda K., Tobitani K., Yao M., Tanaka I., Taguchi S.
NADPH-dependent acetoacetyl-coenzyme A (acetoacetyl-CoA) reductase (PhaB) is a key enzyme in the synthesis of poly(3-hydroxybutyrate) [P(3HB)], along with β-ketothiolase (PhaA) and polyhydroxyalkanoate synthase (PhaC). In this study, PhaB from Ralstonia eutropha was engineered by means of directed ... >> More
NADPH-dependent acetoacetyl-coenzyme A (acetoacetyl-CoA) reductase (PhaB) is a key enzyme in the synthesis of poly(3-hydroxybutyrate) [P(3HB)], along with β-ketothiolase (PhaA) and polyhydroxyalkanoate synthase (PhaC). In this study, PhaB from Ralstonia eutropha was engineered by means of directed evolution consisting of an error-prone PCR-mediated mutagenesis and a P(3HB) accumulation-based in vivo screening system using Escherichia coli. From approximately 20,000 mutants, we obtained two mutant candidates bearing Gln47Leu (Q47L) and Thr173Ser (T173S) substitutions. The mutants exhibited kcat values that were 2.4-fold and 3.5-fold higher than that of the wild-type enzyme, respectively. In fact, the PhaB mutants did exhibit enhanced activity and P(3HB) accumulation when expressed in recombinant Corynebacterium glutamicum. Comparative three-dimensional structural analysis of wild-type PhaB and highly active PhaB mutants revealed that the beneficial mutations affected the flexibility around the active site, which in turn played an important role in substrate recognition. Furthermore, both the kinetic analysis and crystal structure data supported the conclusion that PhaB forms a ternary complex with NADPH and acetoacetyl-CoA. These results suggest that the mutations affected the interaction with substrates, resulting in the acquirement of enhanced activity. << Less
Appl. Environ. Microbiol. 79:6134-6139(2013) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.