3Q99

Structure of neuronal nitric oxide synthase in the ferric state in complex with N~5~-[(3-(ethylsulfanyl)propanimidoyl]-L-ornithine

3Q99 の概要

• エントリーDOI: 10.2210/pdb3q99/pdb
• 関連するPDBエントリー: 3JT4 3Q9A
• 分子名称: Nitric oxide synthase, brain, PROTOPORPHYRIN IX CONTAINING FE, N~5~-[(3-(ethylsulfanyl)propanimidoyl]-L-ornithine, ... (7 entities in total)
• 機能のキーワード: nitric oxide synthase, heme enzyme, oxidoreductase, inhibitor, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Rattus norvegicus (Rat)
• 細胞内の位置: Cell membrane, sarcolemma ; Peripheral membrane protein : P29476
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 100018.74

構造登録者

Li, H.,Doukov, T.,Poulos, T.L. (登録日: 2011-01-07, 公開日: 2011-05-18, 最終更新日: 2023-09-13)

主引用文献

Doukov, T.,Li, H.,Sharma, A.,Martell, J.D.,Soltis, S.M.,Silverman, R.B.,Poulos, T.L.
Temperature-dependent spin crossover in neuronal nitric oxide synthase bound with the heme-coordinating thioether inhibitors.
J.Am.Chem.Soc., 133:8326-8334, 2011

PubMed Abstract: A series of L-arginine analogue nitric oxide synthase inhibitors with a thioether tail have been shown to form an Fe-S thioether interaction as evidenced by continuous electron density between the Fe and S atoms. Even so, the Fe-S thioether interaction was found to be far less important for inhibitor binding than the hydrophobic interactions between the alkyl group in the thioether tail and surrounding protein (Martell et al. J. Am. Chem. Soc. 2010 , 132 , 798). However, among the few thioether inhibitors that showed Fe-S thioether interaction in crystal structures, variations in spin state (high-spin or low-spin) were observed dependent upon the heme iron oxidation state and temperature. Since modern synchrotron X-ray data collection is typically carried out at cryogenic temperatures, we reasoned that some of the discrepancies between cryo-crystal structures and room-temperature UV-visible spectroscopy could be the result of temperature-dependent spin-state changes. We, therefore, have characterized some of these neuronal nitric oxide synthase (nNOS)-thioether inhibitor complexes in both crystal and solution using EPR and UV-visible absorption spectrometry as a function of temperature and the heme iron redox state. We found that some thioether inhibitors switch from high to low spin at lower temperatures similar to the "spin crossover" phenomenon observed in many transition metal complexes.

PubMed: 21534614
DOI: 10.1021/ja201466v

実験手法

X-RAY DIFFRACTION (2.15 Å)