Myoglobin: O2 or not O2襃 that is the question (LB90)

Abstract

Free divers can’t hold their breath as long as whales, but they train their bodies to maximize their oxygen (O2) storing potential using the protein myoglobin. Myoglobin’s structure has been known for decades, but researchers are still trying to determine just how myoglobin functions. Found in muscle tissue, myoglobin stores O2, a molecule needed to produce chemical energy. Toxic ligands, such as carbon monoxide (CO) and cyanide, also bind to myoglobin. When CO binds to a free heme group, the heme's binding affinity for CO is 20,000 times that for O2. When heme is surrounded by myoglobin, that binding affinity ratio drops to only 25. The decrease was thought to be due to steric interactions which prevented CO from occupying the same space as His64. Recent evidence suggests that electrostatic interactions and hydrogen bonds play a more important role. The O2 is stabilized as opposed to the CO being pushed out. Several amino acids (His64, Val68, Phe43, Phe46, and Leu29,) seem to stabilize the ligand. With 3D printing technology, the Brown Deer SMART (Students Modeling a Research Topic) Team created a model of myoglobin. If researchers can fully understand ligand discrimination by heme proteins, not only will divers be able to hold their breath longer, but we may be able to cure diseases like anemia where there is a lack of O2 in the blood. Grant Funding Source: The SMART team program is supported by a grant from NIH‐CTSA.