4YWU

Structural insight into the substrate inhibition mechanism of NADP+-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes

4YWU の概要

• エントリーDOI: 10.2210/pdb4ywu/pdb
• 関連するPDBエントリー: 4OGD 4OHT 4YWV
• 分子名称: Succinic semialdehyde dehydrogenase, 4-oxobutanoic acid, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: succinic semialdehyde dehydrogenase, streptococcus pyogenes, substrate inhibition, es-complex structure, oxidoreductase
• 由来する生物種: Streptococcus pyogenes MGAS1882
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 104310.88

構造登録者

Jang, E.H.,Park, S.A.,Chi, Y.M.,Lee, K.S. (登録日: 2015-03-21, 公開日: 2015-05-06, 最終更新日: 2023-11-08)

主引用文献

Jang, E.H.,Park, S.A.,Chi, Y.M.,Lee, K.S.
Structural insight into the substrate inhibition mechanism of NADP(+)-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes.
Biochem.Biophys.Res.Commun., 461:487-493, 2015

PubMed Abstract: Succinic semialdehyde dehydrogenases (SSADHs) are ubiquitous enzymes that catalyze the oxidation of succinic semialdehyde (SSA) to succinic acid in the presence of NAD(P)(+), and play an important role in the cellular mechanisms including the detoxification of accumulated SSA or the survival in conditions of limited nutrients. Here, we report the inhibitory properties and two crystal structures of SSADH from Streptococcus pyogenes (SpSSADH) in a binary (ES) complex with SSA as the substrate and a ternary (ESS) complex with the substrate SSA and the inhibitory SSA, at 2.4 Å resolution for both structures. Analysis of the kinetic inhibitory parameters revealed significant substrate inhibition in the presence of NADP(+) at concentrations of SSA higher than 0.02 mM, which exhibited complete uncompetitive substrate inhibition with the inhibition constant (Ki) value of 0.10 ± 0.02 mM. In ES-complex of SpSSADH, the SSA showed a tightly bound bent form nearby the catalytic residues, which may be caused by reduction of the cavity volume for substrate binding, compared with other SSADHs. Moreover, structural comparison of ESS-complex with a binary complex with NADP(+) of SpSSADH indicated that the substrate inhibition was induced by the binding of inhibitory SSA in the cofactor-binding site, instead of NADP(+). Our results provide first structure-based molecular insights into the substrate inhibition mechanism of SpSSADH as the Gram-positive bacterial SSADH.

PubMed: 25888791
DOI: 10.1016/j.bbrc.2015.04.047

実験手法

X-RAY DIFFRACTION (2.4 Å)