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[摘要]：Selectivity among NO, CO, and O(2) is crucial for the physiological function of most heme proteins. Although there is a million-fold variation in equilibrium dissociation constants (K(D)), the ratios for NO:CO:O(2) binding stay roughly the same, 1:similar to 10(3):similar to 10(6), when the proximal ligand is a histidine and the distal site is apolar. For these proteins, there is a "sliding scale rule" for plots of log(K(D)) versus ligand type that allows predictions of K(D) values if one or two are missing. The predicted K(D) for binding of O(2) to Ns H-NOX coincides with the value determined experimentally at high pressures. Active site hydrogen bond donors break the rule and selectively increase O(2) affinity with little effect on CO and NO binding. Strong field proximal ligands such as thiolate, tyrosinate, and imidazolate exert a "leveling" effect on ligand binding affinity. The reported picomolar K(D) for binding of NO to sGC deviates even more dramatically from the sliding scale rule, showing a NO:CO K(D) ratio of 1:similar to 10(8). This deviation is explained by a complex, multistep process, in which an initial lowaffinity hexacoordinate NO complex with a measured K(D) of approximate to 54 nM, matching that predicted from the sliding scale rule, is formed initially and then is converted to a high-affinity pentacoordinate complex. This multistep six-coordinate to five-coordinate mechanism appears to be common to all NO sensors that exclude O(2) binding to capture a lower level of cellular NO and prevent its consumption by dioxygenation. |
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