Enzymes
UniProtKB help_outline | 7 proteins |
Reaction participants Show >> << Hide
- Name help_outline (R)-2-hydroxyglutarate Identifier CHEBI:15801 Charge -2 Formula C5H6O5 InChIKeyhelp_outline HWXBTNAVRSUOJR-GSVOUGTGSA-L SMILEShelp_outline O[C@H](CCC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 10 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline A Identifier CHEBI:13193 Charge Formula R SMILEShelp_outline * 2D coordinates Mol file for the small molecule Search links Involved in 2,870 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2-oxoglutarate Identifier CHEBI:16810 (Beilstein: 3664503; CAS: 64-15-3) help_outline Charge -2 Formula C5H4O5 InChIKeyhelp_outline KPGXRSRHYNQIFN-UHFFFAOYSA-L SMILEShelp_outline [O-]C(=O)CCC(=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 425 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline AH2 Identifier CHEBI:17499 Charge 0 Formula RH2 SMILEShelp_outline *([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 2,799 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:38295 | RHEA:38296 | RHEA:38297 | RHEA:38298 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Related reactions help_outline
Specific form(s) of this reaction
Publications
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Structure, substrate specificity, and catalytic mechanism of human D-2-HGDH and insights into pathogenicity of disease-associated mutations.
Yang J., Zhu H., Zhang T., Ding J.
D-2-hydroxyglutarate dehydrogenase (D-2-HGDH) catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) into 2-oxoglutarate, and genetic D-2-HGDH deficiency leads to abnormal accumulation of D-2-HG which causes type I D-2-hydroxyglutaric aciduria and is associated with diffuse large B-cell lymphoma ... >> More
D-2-hydroxyglutarate dehydrogenase (D-2-HGDH) catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) into 2-oxoglutarate, and genetic D-2-HGDH deficiency leads to abnormal accumulation of D-2-HG which causes type I D-2-hydroxyglutaric aciduria and is associated with diffuse large B-cell lymphoma. This work reports the crystal structures of human D-2-HGDH in apo form and in complexes with D-2-HG, D-malate, D-lactate, L-2-HG, and 2-oxoglutarate, respectively. D-2-HGDH comprises a FAD-binding domain, a substrate-binding domain, and a small C-terminal domain. The active site is located at the interface of the FAD-binding domain and the substrate-binding domain. The functional roles of the key residues involved in the substrate binding and catalytic reaction and the mutations identified in D-2-HGDH-deficient diseases are analyzed by biochemical studies. The structural and biochemical data together reveal the molecular mechanism of the substrate specificity and catalytic reaction of D-2-HGDH and provide insights into the pathogenicity of the disease-associated mutations. << Less
Cell Discov. 7:3-3(2021) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Experimental and computational investigation of enzyme functional annotations uncovers misannotation in the EC 1.1.3.15 enzyme class.
Rembeza E., Engqvist M.K.M.
Only a small fraction of genes deposited to databases have been experimentally characterised. The majority of proteins have their function assigned automatically, which can result in erroneous annotations. The reliability of current annotations in public databases is largely unknown; experimental ... >> More
Only a small fraction of genes deposited to databases have been experimentally characterised. The majority of proteins have their function assigned automatically, which can result in erroneous annotations. The reliability of current annotations in public databases is largely unknown; experimental attempts to validate the accuracy within individual enzyme classes are lacking. In this study we performed an overview of functional annotations to the BRENDA enzyme database. We first applied a high-throughput experimental platform to verify functional annotations to an enzyme class of S-2-hydroxyacid oxidases (EC 1.1.3.15). We chose 122 representative sequences of the class and screened them for their predicted function. Based on the experimental results, predicted domain architecture and similarity to previously characterised S-2-hydroxyacid oxidases, we inferred that at least 78% of sequences in the enzyme class are misannotated. We experimentally confirmed four alternative activities among the misannotated sequences and showed that misannotation in the enzyme class increased over time. Finally, we performed a computational analysis of annotations to all enzyme classes in the BRENDA database, and showed that nearly 18% of all sequences are annotated to an enzyme class while sharing no similarity or domain architecture to experimentally characterised representatives. We showed that even well-studied enzyme classes of industrial relevance are affected by the problem of functional misannotation. << Less
PLoS Comput. Biol. 17:e1009446-e1009446(2021) [PubMed] [EuropePMC]
This publication is cited by 9 other entries.
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Two D-2-hydroxy-acid dehydrogenases in Arabidopsis thaliana with catalytic capacities to participate in the last reactions of the methylglyoxal and beta-oxidation pathways.
Engqvist M., Drincovich M.F., Fluegge U.I., Maurino V.G.
The Arabidopsis thaliana locus At5g06580 encodes an ortholog to Saccharomyces cerevisiae d-lactate dehydrogenase (AtD-LDH). The recombinant protein is a homodimer of 59-kDa subunits with one FAD per monomer. A substrate screen indicated that AtD-LDH catalyzes the oxidation of d- and l-lactate, d-2 ... >> More
The Arabidopsis thaliana locus At5g06580 encodes an ortholog to Saccharomyces cerevisiae d-lactate dehydrogenase (AtD-LDH). The recombinant protein is a homodimer of 59-kDa subunits with one FAD per monomer. A substrate screen indicated that AtD-LDH catalyzes the oxidation of d- and l-lactate, d-2-hydroxybutyrate, glycerate, and glycolate using cytochrome c as an electron acceptor. AtD-LDH shows a clear preference for d-lactate, with a catalytic efficiency 200- and 2000-fold higher than that for l-lactate and glycolate, respectively, and a K(m) value for d-lactate of approximately 160 microm. Knock-out mutants showed impaired growth in the presence of d-lactate or methylglyoxal. Collectively, the data indicated that the protein is a d-LDH that participates in planta in the methylglyoxal pathway. Web-based bioinformatic tools revealed the existence of a paralogous protein encoded by locus At4g36400. The recombinant protein is a homodimer of 61-kDa subunits with one FAD per monomer. A substrate screening revealed highly specific d-2-hydroxyglutarate (d-2HG) conversion in the presence of an organic cofactor with a K(m) value of approximately 580 microm. Thus, the enzyme was characterized as a d-2HG dehydrogenase (AtD-2HGDH). Analysis of knock-out mutants demonstrated that AtD-2HGDH is responsible for the total d-2HGDH activity present in A. thaliana. Gene coexpression analysis indicated that AtD-2HGDH is in the same network as several genes involved in beta-oxidation and degradation of branched-chain amino acids and chlorophyll. It is proposed that AtD-2HGDH participates in the catabolism of d-2HG most probably during the mobilization of alternative substrates from proteolysis and/or lipid degradation. << Less
J. Biol. Chem. 284:25026-25037(2009) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.