Interaction of nitric oxide with a functional model of cytochrome c oxidase.
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.
Collman
James P
JP
Department of Chemistry, Stanford University, Stanford, CA 94305, USA. jpc@stanford.edu
Dey
Abhishek
A
Decreau
Richard A
RA
Yang
Ying
Y
Hosseini
Ali
A
Solomon
Edward I
EI
Eberspacher
Todd A
TA
D002248:Carbon Monoxide / Q000378:metabolism; D020134:Catalytic Domain; D003300:Copper / Q000737:chemistry; D003486:Cyanides / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme / Q000737:chemistry; D008954:Models, Biological; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D013053:Spectrophotometry
D003486:Cyanides; D009569:Nitric Oxide; D006418:Heme; D003300:Copper; D002248:Carbon Monoxide; D003576:Electron Transport Complex IV