Nitric oxide (NO), carbon monoxide (CO), and oxygen (O₂) are important physiological messengers whose concentrations vary in a remarkable range, [NO] typically from nM to several μM while [O₂] reaching to hundreds of μM. One of the machineries evolved in living organisms for gas sensing is sensor hemoproteins whose conformational change upon gas binding triggers downstream response cascades. The recently proposed “sliding scale rule” hypothesis provides a general interpretation for gaseous ligand selectivity of hemoproteins, identifying five factors that govern gaseous ligand selectivity. Hemoproteins have intrinsic selectivity for the three gases due to a neutral proximal histidine ligand while proximal strain of heme and distal steric hindrance indiscriminately adjust the affinity of these three gases for heme. On the other hand, multiple-step NO binding and distal hydrogen bond donor(s) specifically enhance affinity for NO and O₂, respectively. The “sliding scale rule” hypothesis provides clear interpretation for dramatic selectivity for NO over O₂ in soluble guanylate cyclase (sGC) which is an important example of sensor hemoproteins and plays vital roles in a wide range of physiological functions. The “sliding scale rule” hypothesis has so far been validated by all experimental data and it may guide future designs for heme-based gas sensors.

一氧化氮 (NO)、一氧化碳 (CO) 和氧气 (O ₂ ) 是重要的生理信使，其浓度变化范围很大，[NO] 通常从 nM 到几 μM，而 [O ₂] 达到数百 μM。在生物体中进化出的气体传感机制之一是传感器血红蛋白，其在气体结合时的构象变化会触发下游响应级联。最近提出的“滑动比例法则”假设为血红素蛋白的气态配体选择性提供了一般解释，确定了控制气态配体选择性的五个因素。由于中性的近端组氨酸配体，血红素蛋白对这三种气体具有固有的选择性，而近端血红素应变和远端位阻会不加选择地调整这三种气体对血红素的亲和力。另一方面，多步 NO 结合和远端氢键供体特异性增强对 NO 和 O _{2 的}亲和力， 分别。“滑动比例法则”假设为可溶性鸟苷酸环化酶 (sGC) 中NO 对 O _{2 的}显着选择性提供了清晰的解释，sGC 是传感器血红蛋白的一个重要例子，在广泛的生理功能中起着至关重要的作用。迄今为止，所有实验数据都验证了“滑动比例规则”假设，它可以指导基于血红素的气体传感器的未来设计。