6ES9

Methylsuccinyl-CoA dehydrogenase of Paracoccus denitrificans with bound flavin adenine dinucleotide

6ES9 の概要

• エントリーDOI: 10.2210/pdb6es9/pdb
• 分子名称: Acyl-CoA dehydrogenase, SULFATE ION, COENZYME A, ... (5 entities in total)
• 機能のキーワード: methylsuccinyl-coa, acyl-coa dehydrogenase, flavin adenine dinucleotide, ethylmalonyl-coa pathway, flavoprotein
• 由来する生物種: Paracoccus denitrificans (strain Pd 1222)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123460.75

構造登録者

Zarzycki, J.,Schwander, T.,Erb, T.J. (登録日: 2017-10-19, 公開日: 2018-01-03, 最終更新日: 2024-11-13)

主引用文献

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

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: 29275330
DOI: 10.1074/jbc.RA117.000764

実験手法

X-RAY DIFFRACTION (1.37 Å)