Enzymes
UniProtKB help_outline | 1 proteins |
Enzyme class help_outline |
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Reaction participants Show >> << Hide
- Name help_outline (2S)-methylsuccinyl-CoA Identifier CHEBI:84866 Charge -5 Formula C26H37N7O19P3S InChIKeyhelp_outline OUFHQHVVFSERRI-VKBDFPRVSA-I SMILEShelp_outline C[C@@H](CC([O-])=O)C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(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 2D coordinates Mol file for the small molecule Search links Involved in 2 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 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
oxidized [electron-transfer flavoprotein]
Identifier
RHEA-COMP:10685
Reactive part
help_outline
- Name help_outline FAD Identifier CHEBI:57692 Charge -3 Formula C27H30N9O15P2 InChIKeyhelp_outline IMGVNJNCCGXBHD-UYBVJOGSSA-K SMILEShelp_outline Cc1cc2nc3c(nc(=O)[n-]c3=O)n(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(=O)OP([O-])(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n3cnc4c(N)ncnc34)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 170 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2-methylfumaryl-CoA Identifier CHEBI:75635 Charge -5 Formula C26H35N7O19P3S InChIKeyhelp_outline LVBVWNJPMXCQJE-CBBDEUQJSA-I SMILEShelp_outline C\C(=C/C([O-])=O)C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(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 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
reduced [electron-transfer flavoprotein]
Identifier
RHEA-COMP:10686
Reactive part
help_outline
- Name help_outline FADH2 Identifier CHEBI:58307 Charge -2 Formula C27H33N9O15P2 InChIKeyhelp_outline YPZRHBJKEMOYQH-UYBVJOGSSA-L SMILEShelp_outline Cc1cc2Nc3c([nH]c(=O)[nH]c3=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(=O)OP([O-])(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n3cnc4c(N)ncnc34)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 161 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:45028 | RHEA:45029 | RHEA:45030 | RHEA:45031 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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(2S)-Methylsuccinyl-CoA dehydrogenase closes the ethylmalonyl-CoA pathway for acetyl-CoA assimilation.
Erb T.J., Fuchs G., Alber B.E.
Many organic substrates are metabolized via acetyl-coenzyme A (CoA) and enter central carbon metabolism at the level of this compound. We recently described the outlines of the ethylmalonyl-CoA pathway, a new acetyl-CoA assimilation strategy that operates in a number of bacteria such as Rhodobacte ... >> More
Many organic substrates are metabolized via acetyl-coenzyme A (CoA) and enter central carbon metabolism at the level of this compound. We recently described the outlines of the ethylmalonyl-CoA pathway, a new acetyl-CoA assimilation strategy that operates in a number of bacteria such as Rhodobacter sphaeroides, Methylobacterium extorquens and streptomycetes and replaces the glyoxylate cycle. This new pathway involves a unique central reaction sequence catalysed by characteristic enzymes. Here, we identified and characterized (2S)-methylsuccinyl-CoA dehydrogenase from R. sphaeroides, a flavin adenine dinucleotide-containing enzyme that catalyses the last unknown step in the central part of the ethylmalonyl-CoA pathway, the oxidation of (2S)-methylsuccinyl-CoA to mesaconyl-(C1)-CoA. This enzyme is highly specific for its substrate and forms a distinct subgroup within the superfamily of flavin-dependent acyl-CoA dehydrogenases. Homology modelling and comparative sequence analyses with well-studied members of this superfamily identified amino acids that may contribute to the narrow substrate specificity of (2S)-methylsuccinyl-CoA dehydrogenase. The central part of the ethylmalonyl-CoA pathway was reconstituted in vitro using four recombinant enzymes. By this work, the ethylmalonyl-CoA pathway and its stereochemical course have been completely solved. This allowed defining the minimum set of enzymes necessary for its operation and to screen for further organisms following this acetyl-CoA assimilation strategy. << Less
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Structural basis for substrate specificity of methylsuccinyl-CoA dehydrogenase, an unusual member of the acyl-CoA dehydrogenase family.
Schwander T., McLean R., Zarzycki J., Erb T.J.
(2<i>S</i>)-methylsuccinyl-CoA dehydrogenase (MCD) belongs to the family of FAD-dependent acyl-CoA dehydrogenase (ACD) and is a key enzyme of the ethylmalonyl-CoA pathway for acetate assimilation. It catalyzes the oxidation of (2<i>S</i>)-methylsuccinyl-CoA to α,β-unsaturated mesaconyl-CoA and sho ... >> More
(2<i>S</i>)-methylsuccinyl-CoA dehydrogenase (MCD) belongs to the family of FAD-dependent acyl-CoA dehydrogenase (ACD) and is a key enzyme of the ethylmalonyl-CoA pathway for acetate assimilation. It catalyzes the oxidation of (2<i>S</i>)-methylsuccinyl-CoA to α,β-unsaturated mesaconyl-CoA and shows only about 0.5% activity with succinyl-CoA. Here we report the crystal structure of MCD at a resolution of 1.37 Å. The enzyme forms a homodimer of two 60-kDa subunits. Compared with other ACDs, MCD contains an ∼170-residue-long N-terminal extension that structurally mimics a dimer-dimer interface of these enzymes that are canonically organized as tetramers. MCD catalyzes the unprecedented oxidation of an α-methyl branched dicarboxylic acid CoA thioester. Substrate specificity is achieved by a cluster of three arginines that accommodates the terminal carboxyl group and a dedicated cavity that facilitates binding of the C2 methyl branch. MCD apparently evolved toward preventing the nonspecific oxidation of succinyl-CoA, which is a close structural homolog of (2<i>S</i>)-methylsuccinyl-CoA and an essential intermediate in central carbon metabolism. For different metabolic engineering and biotechnological applications, however, an enzyme that can oxidize succinyl-CoA to fumaryl-CoA is sought after. Based on the MCD structure, we were able to shift substrate specificity of MCD toward succinyl-CoA through active-site mutagenesis. << Less