title: A "sliding scale rule" for selectivity among NO, CO, and O₂ by heme protein sensors.
abstract: 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:~10(3):~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 O₂to 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 "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:~10(8). This deviation is explained by a complex, multistep process, in which an initial low-affinity hexacoordinate NO complex with a measured K(D) of ≈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 O₂ binding to capture a lower level of cellular NO and prevent its consumption by dioxygenation.
authors: Division of Hematology, Internal Medicine, University of Texas Medical School at Houston, Houston, Texas 77030, United States. Ah-lim.tsai@uth.tmc.edu
authors: Ah-Lim
authors: AL
authors: Tsai
authors: Vladimir
authors: V
authors: Berka
authors: Emil
authors: E
authors: Martin
authors: John S
authors: JS
authors: Olson
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002248:Carbon Monoxide / Q000737:chemistry* / Q000378:metabolism; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D046937:Nostoc / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D001426:Bacterial Proteins; D006420:Hemeproteins; D008024:Ligands; D009569:Nitric Oxide; D002248:Carbon Monoxide; D010100:Oxygen