The interaction of microsomal cytochrome P450 2B4 with its redox partners, cytochrome P450 reductase and cytochrome b(5).
The interaction of microsomal cytochrome P450 2B4 with its redox partners, cytochrome P450 reductase and cytochrome b(5).
复制标题
DOI：
10.1016/j.abb.2010.10.023
复制
发表时间：
2011-03-01
影响因子：
3.9
通讯作者：
Waskell L
中科院分区：
文献类型：
--
作者：
Im SC;Waskell L
1 .细胞色素P450 2B4是一种微粒体蛋白，具有多步反应周期，类似于在大多数其他细胞色素P450中观察到的。细胞色素P450 - 2b4 -底物配合物通过细胞色素P450还原酶从铁形式还原为亚铁形式。结合氧后，氧化亚铁蛋白接受由细胞色素P450还原酶或细胞色素b5提供的第二个电子。在这两种情况下，都会形成产物。当第二个电子由细胞色素b5提供时，催化（产物形成）比存在细胞色素P450还原酶时快10到100倍。这减少了副产物形成（过氧化氢和超氧化物）的时间，并将NADPH消耗与产物形成的偶联性提高了约15%。细胞色素b5也被证明与细胞色素P450还原酶竞争细胞色素P450 2B4近端表面的一个结合位点。细胞色素b5对细胞色素P450 2B4反应性的这两种不同作用可以解释细胞色素b5如何能够刺激、抑制或不影响细胞色素P450 2B4活性。当细胞色素b5与细胞色素P450还原酶的摩尔比较低（<1）时，更快的催化作用导致底物代谢增强。相反，在细胞色素b5与细胞色素P450还原酶的高摩尔比（>）下，细胞色素b5通过结合到细胞色素P450的近端表面来抑制活性，阻止还原酶将含铁的细胞色素P450还原为含铁蛋白，从而终止催化反应循环。当细胞色素b5的刺激和抑制作用相等时，它似乎对酶的活性没有影响。据推测，细胞色素b5通过引起活性位点的构象变化来刺激催化作用，这使得细胞色素P450的活性氧化氧铁基物种比还原酶存在时形成得更快。
1 Cytochrome P450 2B4 is a microsomal protein with a multi-step reaction cycle similar to that observed in the majority of other cytochromes P450. The cytochrome P450 2B4-substrate complex is reduced from the ferric to the ferrous form by cytochrome P450 reductase. After binding oxygen, the oxyferrous protein accepts a second electron which is provided by either cytochrome P450 reductase or cytochrome b5. In both instances, product formation occurs. When the second electron is donated by cytochrome b5, catalysis (product formation) is ∼ 10 to 100-fold faster than in the presence of cytochrome P450 reductase. This allows less time for side product formation (hydrogen peroxide and superoxide) and improves by ∼ 15% the coupling of NADPH consumption to product formation. Cytochrome b5 has also been shown to compete with cytochrome P450 reductase for a binding site on the proximal surface of cytochrome P450 2B4. These two different effects of cytochrome b5 on cytochrome P450 2B4 reactivity can explain how cytochrome b5 is able to stimulate, inhibit, or have no effect on cytochrome P450 2B4 activity. At low molar ratios (<1) of cytochrome b5 to cytochrome P450 reductase, the more rapid catalysis results in enhanced substrate metabolism. In contrast, at high molar ratios (>1) of cytochome b5 to cytochrome P450 reductase, cytochrome b5 inhibits activity by binding to the proximal surface of cytochrome P450 and preventing the reductase from reducing ferric cytochrome P450 to the ferrous protein, thereby aborting the catalytic reaction cycle. When the stimulatory and inhibitory effects of cytochrome b5 are equal, it will appear to have no effect on the enzymatic activity. It is hypothesized that cytochrome b5 stimulates catalysis by causing a conformational change in the active site, which allows the active oxidizing oxyferryl species of cytochrome P450 to be formed more rapidly than in the presence of reductase.
登录
查看更多内容
影响因子：
5.8
作者：
CANOVADAVIS, E;CHIANG, JYL;WASKELL, L
通讯作者：
WASKELL, L
影响因子：
4.8
作者：
Bridges, A;Gruenke, L;Waskell, L
通讯作者：
Waskell, L
影响因子：
158.5
作者：
HEGESH, E;HEGESH, J;KAFTORY, A
通讯作者：
KAFTORY, A
影响因子：
2.9
作者：
Gruenke, LD;Sun, J;Waskell, L
通讯作者：
Waskell, L
影响因子：
3.9
作者：
KATAGIRI, M;KAGAWA, N;WATERMAN, MR
通讯作者：
WATERMAN, MR