6ES9
Methylsuccinyl-CoA dehydrogenase of Paracoccus denitrificans with bound flavin adenine dinucleotide
Summary for 6ES9
| Entry DOI | 10.2210/pdb6es9/pdb |
| Descriptor | Acyl-CoA dehydrogenase, SULFATE ION, COENZYME A, ... (5 entities in total) |
| Functional Keywords | methylsuccinyl-coa, acyl-coa dehydrogenase, flavin adenine dinucleotide, ethylmalonyl-coa pathway, flavoprotein |
| Biological source | Paracoccus denitrificans (strain Pd 1222) |
| Total number of polymer chains | 2 |
| Total formula weight | 123460.75 |
| Authors | Zarzycki, J.,Schwander, T.,Erb, T.J. (deposition date: 2017-10-19, release date: 2018-01-03, Last modification date: 2024-11-13) |
| Primary citation | Schwander, T.,McLean, R.,Zarzycki, J.,Erb, T.J. Structural basis for substrate specificity of methylsuccinyl-CoA dehydrogenase, an unusual member of the acyl-CoA dehydrogenase family. J. Biol. Chem., 293:1702-1712, 2018 Cited by PubMed Abstract: (2)-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)-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)-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. PubMed: 29275330DOI: 10.1074/jbc.RA117.000764 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.37 Å) |
Structure validation
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