5X9D

Crystal structure of homoserine dehydrogenase in complex with L-cysteine and NAD

5X9D の概要

• エントリーDOI: 10.2210/pdb5x9d/pdb
• 関連するPDBエントリー: 4YDR 5AVO
• 分子名称: Homoserine dehydrogenase, (2R)-3-[[(4S)-3-aminocarbonyl-1-[(2R,3R,4S,5R)-5-[[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-3,4-bis(oxidanyl)oxolan-2-yl]-4H-pyridin-4-yl]sulfanyl]-2-azanyl-propanoic acid, L(+)-TARTARIC ACID, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, complex, inhibitor
• 由来する生物種: Sulfolobus tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34346.17

構造登録者

Goto, M.,Ogata, K.,Kaneko, R.,Yoshimune, K. (登録日: 2017-03-06, 公開日: 2018-05-02, 最終更新日: 2024-10-16)

主引用文献

Ogata, K.,Yajima, Y.,Nakamura, S.,Kaneko, R.,Goto, M.,Ohshima, T.,Yoshimune, K.
Inhibition of homoserine dehydrogenase by formation of a cysteine-NAD covalent complex
Sci Rep, 8:5749-5749, 2018

PubMed Abstract: Homoserine dehydrogenase (EC 1.1.1.3, HSD) is an important regulatory enzyme in the aspartate pathway, which mediates synthesis of methionine, threonine and isoleucine from aspartate. Here, HSD from the hyperthermophilic archaeon Sulfolobus tokodaii (StHSD) was found to be inhibited by cysteine, which acted as a competitive inhibitor of homoserine with a Ki of 11 μM and uncompetitive an inhibitor of NAD and NADP with Ki's of 0.55 and 1.2 mM, respectively. Initial velocity and product (NADH) inhibition analyses of homoserine oxidation indicated that StHSD first binds NAD and then homoserine through a sequentially ordered mechanism. This suggests that feedback inhibition of StHSD by cysteine occurs through the formation of an enzyme-NAD-cysteine complex. Structural analysis of StHSD complexed with cysteine and NAD revealed that cysteine situates within the homoserine binding site. The distance between the sulfur atom of cysteine and the C4 atom of the nicotinamide ring was approximately 1.9 Å, close enough to form a covalent bond. The UV absorption-difference spectrum of StHSD with and without cysteine in the presence of NAD, exhibited a peak at 325 nm, which also suggests formation of a covalent bond between cysteine and the nicotinamide ring.

PubMed: 29636528
DOI: 10.1038/s41598-018-24063-1

実験手法

X-RAY DIFFRACTION (2.1 Å)