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生醫所105-2專題演講活動，敬邀 美國德州大學休士頓醫學中心內科 蔡亞麟教授進行專題演講
演講主題為：
How do heme proteins discriminate the smallest biological molecules: CO, NO and O2? --------- road to resolve a 40-year old puzzle about the mechanism of soluble guanylyl cyclase.
Abstract
CO, NO and O2 are involved in many critical biological functions and diseases. They have similar size, solubility and differs only by one valence electron. Biological activities of these smallest molecules are mainly delivered via interaction with various hemeproteins. Discrimination between CO, NO and O2 is evolved in many hemeproteins as the most fundamental mechanisms in gas transport, storage and sensing. The most dramatic example is soluble guanylyl cyclase (sGC), the key enzyme responsible for conversion from GTP to the second messenger cyclic GMP (cGMP). This heterodimeric hemeprotein is the unique and authentic NO sensor in mammalian systems. When NO binds to the heme ��-subunit (apparent KD is ~ pM), it enhances the activity of cGMP formation to hundred folds above the basal level. Yet, CO binding to sGC only shows minor activity increase, and O2 is completely inert. The underlying mechanism of such dramatic discrimination between these three gases has been an enigma for 40 years. Our recent kinetic study and bioinformatic graphical analysis of hundreds hemeproteins and model compounds between their binding affinity and ligand types disclosed the truth and revealed five key factors that modulate the gas ligand selectivity. This general paradigm has been coined as “Sliding Scale Rule” hypothesis. So far, this theory is successful in interpreting the gas ligand discriminating power against three gases of every tested hemeprotein. Understanding the fundamental mechanism of ligand selectivity has major impact in deciphering nature’s design for sGC to function as a bona fide NO heme sensor, and has the potential in designing novel heme-based sensors. (Supported by NIH HL095820, NS094535)
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