氧化物输送和黑姆辅助的S-化由床尼特罗福林的床
Hemant B Badgandi1, Andrzej Weichsel1, William R Montfort1
1Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States of America.
Journal of inorganic biochemistry
|June 8, 2023
概括
虫酸 (cNP) 通过一种与氨酸结合的血释放氧化 (NO). 这项研究表明,虽然Fe (II) -NO形成,但SNO形成被醇结合抑制,这表明它不会发生在唾液腺中.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 昆虫生理学 昆虫生理学
背景情况:
- 尼特罗福林是食血昆虫中的血红蛋白,可提供氧化 (NO) 诱导血管扩张并抑制血小板聚合.
- Cimex lectularius nitrophorin (cNP) 使用一种与氨酸结合的铁 (Fe(III)) 血和释放NO作为血液养期间pH值变化的反应.
- 之前的研究表明,cNP可以化其近位半氨酸,形成S-氨酸半氨酸 (SNO),这一过程可能涉及血减少.
研究的目的:
- 阐明cNP中SNO形成的机制.
- 研究影响NO结合和SNO形成的结构和化学因素.
- 确定SNO形成在昆虫唾液腺功能背景下的生理相关性.
主要方法:
- 确定了暴露于NO的化学降解cNP的1.6 Å晶体结构.
- 在突变的cNP变体上使用了晶体和光谱方法.
- 进行了实验,以评估NO结合和SNO形成的pH依赖.
主要成果:
- 晶体结构证实了暴露于NO的减少cNP中的Fe (II) -NO的形成,但不是SNO,支持金属辅助的SNO形成机制.
- 在cNP的近端部位的固体阻碍抑制了SNO的形成,而更放松的部位增强了它,表明这种修饰的特异性.
- 较低的pH值有利于 thiol-heme 结合,增加 NO 亲和力 (Kd = 70 nM),但干扰 SNO 的形成.
结论:
- 对于NO结合而言,金属辅助的Fe (III) 降解为Fe (II) 是至关重要的,但在这些条件下没有观察到SNO的形成.
- 靠近的半氨酸中的固体因素显著影响SNO形成的特异性.
- 在酸性pH下提-结合增强了NO的结合,但阻止了SNO的形成,这表明cNP-SNO不太可能在昆虫的唾液腺中形成.
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