3MI3

Homocitrate Synthase Lys4 bound to Lysine

「3L90」から置き換えられました

3MI3 の概要

• エントリーDOI: 10.2210/pdb3mi3/pdb
• 関連するPDBエントリー: 3IVS 3IVT 3IVU
• 分子名称: Homocitrate synthase, mitochondrial, LYSINE, ZINC ION, ... (5 entities in total)
• 機能のキーワード: tim barrel, metalloprotein, transferase, claisen condensation, amino-acid biosynthesis, lysine biosynthesis
• 由来する生物種: Schizosaccharomyces pombe (Fission yeast)
• 細胞内の位置: Mitochondrion (Potential): Q9Y823
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93981.17

構造登録者

Bulfer, S.L.,Scott, E.M.,Pillus, L.,Trievel, R.C. (登録日: 2010-04-09, 公開日: 2010-04-28, 最終更新日: 2023-09-06)

主引用文献

Bulfer, S.L.,Scott, E.M.,Pillus, L.,Trievel, R.C.
Structural Basis for L-lysine Feedback Inhibition of Homocitrate Synthase
J.Biol.Chem., 285:10446-10453, 2010

PubMed Abstract: The alpha-aminoadipate pathway of lysine biosynthesis is modulated at the transcriptional and biochemical levels by feedback inhibition. The first enzyme in the alpha-aminoadipate pathway, homocitrate synthase (HCS), is the target of the feedback regulation and is strongly inhibited by l-lysine. Here we report the structure of Schizosaccharomyces pombe HCS (SpHCS) in complex with l-lysine. The structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for binding within the active site of HCS. Differential recognition of the substrate and inhibitor is achieved via a switch position within the (alpha/beta)(8) TIM barrel of the enzyme that can distinguish between the C5-carboxylate group of 2-oxoglutarate and the epsilon-ammonium group of l-lysine. In vitro and in vivo assays demonstrate that mutations of the switch residues, which interact with the l-lysine epsilon-ammonium group, abrogate feedback inhibition, as do substitutions of residues within the C-terminal domain that were identified in a previous study of l-lysine-insensitive HCS mutants in Saccharomyces cerevisiae. Together, these results yield new insights into the mechanism of feedback regulation of an enzyme central to lysine biosynthesis.

PubMed: 20089861

実験手法

X-RAY DIFFRACTION (2.38 Å)