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Structure effect of water-soluble iron porphyrins on catalyzing protein tyrosine nitration in the presence of nitrite and hydrogen peroxide.
Nitric Oxide ( IF 3.9 ) Pub Date : 2019-07-24 , DOI: 10.1016/j.niox.2019.07.007
Jiayu Li 1 , Zhen Yang 2 , Hailing Li 1 , Zhonghong Gao 1
Affiliation  

Water-soluble iron porphyrins, such as FeTPPS (5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III)), FeTMPyP (5,10,15,20-tetrakis (N-methyl-4'-pyridyl) porphyrinato iron (III) chloride) and FeTBAP (5,10,15,20-tetrakis (4-benzoic acid) porphyrinato iron (III)), are highly active catalysts for peroxynitrite decomposition and thereby have been suggested as therapeutic agent for inflammatory diseases that implicate the involvement of nitrotyrosine formation. Here, we systemically investigated catalytic properties of FeTPPS, FeTMPyP and FeTBAP on protein nitration in the presence of hydrogen peroxide and nitrite. We showed that FeTPPS, FeTBAP and FeTMPyP all exhibited higher peroxidase activity in compared with hemin. As to protein nitration, the catalytic effect of FeTPPS and FeTBAP are effective in the presence of hydrogen peroxide and nitrite, while negligible BSA nitration was observed in the case of FeTMPyP. Moreover, the underlying mechanism of the oxidation of FeTPPS, FeTBAP and FeTMPyP was further studied. Collectively, our results suggest that, compound I and II species are involved in as the key intermediates in FeTMPyP/H2O2 system as similar as those in FeTPPS/H2O2 and FeTBAP/H2O2 system. As compared to weak antioxidants, TPPS and TBAP, however, TMPyP scavenges oxo-Fe (IV) intermediates of FeTMPyP at a faster rate by significant self-degradation; results in the shortest lifetimes of OFeIV-TMPyP and the lowest catalytic activity on oxidizing tyrosine and nitrite; and therefore, attributes to inactivation of FeTMPyP in protein nitration. In addition, association of FeTMPyP to BSA was found weak, while strong binding of FeTPPS and FeTBAP were observed. The weak binding keeps away of target residue of BSA from the center of FeTMPyP where the RNS is generated, which might be attributed as additional factors to the inactivation of FeTMPyP in protein nitration.

中文翻译:

水溶性亚铁卟啉在亚硝酸盐和过氧化氢存在下催化蛋白质酪氨酸硝化的结构效应。

水溶性卟啉铁,例如FeTPPS(5,10,15,20-四(4-磺酰基苯基)卟啉铁(III)),FeTMPyP(5,10,15,20-四(N-甲基-4'-吡啶基)卟啉铁(III)氯化物和FeTBAP(5,10,15,20-四(4-苯甲酸)卟啉铁(III))是用于过氧亚硝酸盐分解的高活性催化剂,因此被建议用作治疗亚硝酸盐的治疗剂涉及硝基酪氨酸形成的炎性疾病。在这里,我们系统地研究了FeTPPS,FeTMPyP和FeTBAP在过氧化氢和亚硝酸盐存在下对蛋白质硝化的催化性能。我们表明,与血红素相比,FeTPPS,FeTBAP和FeTMPyP均表现出更高的过氧化物酶活性。至于蛋白质硝化 FeTPPS和FeTBAP的催化作用在过氧化氢和亚硝酸盐存在下有效,而FeTMPyP的BSA硝化作用可忽略不计。此外,还进一步研究了FeTPPS,FeTBAP和FeTMPyP氧化的潜在机理。总的来说,我们的结果表明,与FeTPPS / H2O2和FeTBAP / H2O2系统中的化合物相似,化合物I和II物种是FeTMPyP / H2O2系统中的关键中间体。与弱抗氧化剂TPPS和TBAP相比,TMPyP通过显着的自降解以更快的速度清除FeTMPyP的氧-铁(IV)中间体。导致OFeIV-TMPyP的寿命最短,并且对氧化酪氨酸和亚硝酸盐的催化活性最低;因此,归因于蛋白质硝化过程中FeTMPyP的失活。此外,发现FeTMPyP与BSA的结合较弱,而观察到FeTPPS和FeTBAP的强结合。弱结合使BSA的目标残基远离产生RNS的FeTMPyP中心,这可能归因于蛋白质硝化中FeTMPyP失活的其他因素。
更新日期:2019-11-01
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