化物由髓氧化酶结合是由通道动态和电荷相互作用来调节的
Urban Leitgeb1, Radek Crha2, Isabella Fegerl1
1Institute of Biochemistry, Department of Natural Sciences and Sustainable Resources, BOKU University, Vienna, Muthgasse 18, Vienna, Austria.
骨髓氧化酶 (MPO) 使用化物杀死细菌. 新的研究揭示了离子和充电残留物促进化物进入MPO活性部位,澄清了其免疫防御机制.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 骨髓氧化酶 (MPO) 对于天生的免疫力至关重要,产生杀菌酸.
- 现有的数据不足以解释MPO的化物氧化机制,pH依赖性和活性部位.
- 希斯蒂丁261的非典型pKa和化物结合位点结构仍然不清楚.
研究的目的:
- 通过MPO阐明化物氧化机制.
- 调查活性部位残留物和离子在化物结合中的作用.
- 澄清管理MPO职能的结构性和动态因素.
主要方法:
- MPO-化物复合物的X射线晶体学.
- 分子动力学模拟.分子动力学模拟.
- 动力学分析.
主要成果:
- 化物集成到水网络中,在不同的pH值下不直接结合histidine 261.
- 丁261质子化增加了活性部位的灵活性,有助于阿金宁405的运动.
- 离子作为电荷屏蔽,促进化物通过接入通道运输.
结论:
- 化物进入MPO的活性部位是通过静电相互作用来调节的.
- 保存的水分子和充电的残留物介于化物结合和氧化.
- 这项研究阐明了MPO在先天免疫防御中的机制.
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