Collman James P, Dey Abhishek, Decreau Richard A, Yang Ying, Hosseini Ali, Solomon Edward I, Eberspacher Todd A
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):9892-6. doi: 10.1073/pnas.0804257105. Epub 2008 Jul 16.
Cytochrome c oxidase (CcO) is a multimetallic enzyme that carries out the reduction of O2 to H2O and is essential to respiration, providing the energy that powers all aerobic organisms by generating heat and forming ATP. The oxygen-binding heme a(3) should be subject to fatal inhibition by chemicals that could compete with O2 binding. Near the CcO active site is another enzyme, NO synthase, which produces the gaseous hormone NO. NO can strongly bind to heme a(3), thus inhibiting respiration. However, this disaster does not occur. Using functional models for the CcO active site, we show how NO inhibition is avoided; in fact, it is found that NO can protect the respiratory enzyme from other inhibitors such as cyanide, a classic poison.
细胞色素c氧化酶（CcO）是一种多金属酶，负责将O2还原为H2O，对呼吸作用至关重要，通过产生热量和形成ATP为所有需氧生物提供能量。与O2结合的血红素a(3)应该会受到能够与O2结合竞争的化学物质的致命抑制。在CcO活性位点附近还有另一种酶，即一氧化氮合酶，它会产生气态激素NO。NO能强烈结合血红素a(3)，从而抑制呼吸作用。然而，这种灾难并未发生。通过使用CcO活性位点的功能模型，我们展示了如何避免NO抑制；事实上，发现NO可以保护呼吸酶免受其他抑制剂（如经典毒物氰化物）的影响。
