The hemerythrin-like diiron protein from Mycobacterium kansasii is a nitric oxide peroxidase.
The hemerythrin-like diiron protein from Mycobacterium kansasii is a nitric oxide peroxidase.
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DOI：
10.1016/j.jbc.2022.101696
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Davidson VL
中科院分区：
文献类型：
--
作者：
Ma Z;Holland AA;Szlamkowicz I;Anagnostopoulos V;Caldas Nogueira ML;Caranto JD;Davidson VL
来自堪萨斯分枝杆菌 (Mka HLP) 的血红蛋白样蛋白是一类独特的氧桥二铁蛋白的成员，这种蛋白仅存在于导致人类呼吸系统疾病的分枝杆菌物种中。由于它表现出较弱的过氧化氢酶活性，并且暴露于一氧化氮 (NO) 时吸光度会发生变化，因此在多种条件下检查了 Mka HLP 对 NO 的反应性。在厌氧条件下，我们发现 NO 通过吸收 520 nm 光的中间体转化为亚硝酸盐 (NO2−)。在有氧条件下，NO 转化为硝酸盐 (NO3−)。在这两种情况中，所形成的亚硝酸盐或硝酸盐的最大量至多与Mka HLP的浓度是化学计量的。当与 NO 和 H2O2 一起孵育时，我们观察到 NO 过氧化物酶活性产生亚硝酸盐和水作为反应产物。该反应过程中 NO 消耗的稳态动力学分析得出 NO 的 Km 为 0.44 μM，kcat/Km 为 2.3 × 105 M−1s−1。这种对 NO 的高亲和力与 Mka HLP 在阻止亚硝化应激中的生理作用一致。这是使用氧桥二铁中心的过氧化物酶的第一个例子，也是利用 NO 作为电子供体和共底物的过氧化物酶的罕见例子。这种活性提供了一种机制，传染性分枝杆菌可以对抗巨噬细胞产生的 NO 和超氧化物 (O2−) 混合物，以防御细菌，并产生 NO2− 以适应缺氧条件。
The hemerythrin-like protein from Mycobacterium kansasii (Mka HLP) is a member of a distinct class of oxo-bridged diiron proteins that are found only in mycobacterial species that cause respiratory disorders in humans. Because it had been shown to exhibit weak catalase activity and a change in absorbance on exposure to nitric oxide (NO), the reactivity of Mka HLP toward NO was examined under a variety of conditions. Under anaerobic conditions, we found that NO was converted to nitrite (NO2−) via an intermediate, which absorbed light at 520 nm. Under aerobic conditions NO was converted to nitrate (NO3−). In each of these two cases, the maximum amount of nitrite or nitrate formed was at best stoichiometric with the concentration of Mka HLP. When incubated with NO and H2O2, we observed NO peroxidase activity yielding nitrite and water as reaction products. Steady-state kinetic analysis of NO consumption during this reaction yielded a Km for NO of 0.44 μM and a kcat/Km of 2.3 × 105 M−1s−1. This high affinity for NO is consistent with a physiological role for Mka HLP in deterring nitrosative stress. This is the first example of a peroxidase that uses an oxo-bridged diiron center and a rare example of a peroxidase utilizing NO as an electron donor and cosubstrate. This activity provides a mechanism by which the infectious Mycobacterium may combat against the cocktail of NO and superoxide (O2•−) generated by macrophages to defend against bacteria, as well as to produce NO2− to adapt to hypoxic conditions.
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DOI：
10.1073/pnas.95.18.10378
发表时间：
1998-09-01
影响因子：
11.1
作者：
Gardner, PR;Gardner, AM;Salzman, AL
通讯作者：
Salzman, AL
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
影响因子：
4.3
作者：
Lo, Feng-Chun;Hsieh, Chang-Chih;Liaw, Wen-Feng
通讯作者：
Liaw, Wen-Feng
影响因子：
3.7
作者：
Alvarez-Carreño C;Becerra A;Lazcano A
通讯作者：
Lazcano A
影响因子：
30.3
作者：
Rohde, Kyle H.;Abramovitch, Robert B.;Russell, David G.
通讯作者：
Russell, David G.