A 鈥淪liding Scale Rule鈥?for Selectivity among NO, CO, and O2 by Heme Protein Sensors

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• 作者：Ah-Lim Tsai ; Vladimir Berka ; Emil Martin ; John S. Olson
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：January 10, 2012
• 年：2012
• 卷：51
• 期：1
• 页码：172-186
• 全文大小：734K
• 年卷期：v.51,no.1(January 10, 2012)
• ISSN：1520-4995

文摘

Selectivity among NO, CO, and O₂ 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:O₂ binding stay roughly the same, 1:10³:10⁶, when the proximal ligand is a histidine and the distal site is apolar. For these proteins, there is a 鈥渟liding scale rule鈥?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 O₂ to Ns H-NOX coincides with the value determined experimentally at high pressures. Active site hydrogen bond donors break the rule and selectively increase O₂ affinity with little effect on CO and NO binding. Strong field proximal ligands such as thiolate, tyrosinate, and imidazolate exert a 鈥渓eveling鈥?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 1:10⁸. This deviation is explained by a complex, multistep process, in which an initial low-affinity hexacoordinate NO complex with a measured K_D of 鈮?4 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 O₂ binding to capture a lower level of cellular NO and prevent its consumption by dioxygenation.