Apr 9, 2018
Prof. Eric Block
The mechanisms by which muscone and analogs produce the aroma known as musk, a common component of perfumes, were reported by the research team.
UCLA Visiting Scholar Professor Eric Block (University at Albany, State University of New York) and collaborators Victor Batista (Yale University), David O’Hagan (St. Andrews University, Scotland) and Hanyi Zhuang (Shanghai Jiao Tong University) combined computational and experimental approaches to examine the activation of two recently identified human musk receptors, OR5AN1 and OR1A1. Their research was featured in the current issue of the Proceedings of the National Academy of Science.
Musk, an important component of perfumes since ancient times and represented here by key component (R)-muscone, has been found to bind to amino acid tyrosine 260 of the human olfactory receptor OR5AN1, providing an insight into the molecular basis for olfaction.
The research team developed a three-dimensional model of the musk receptors using a quantum mechanics/molecular mechanics molecular simulation method that enables the study of chemical processes in solution and in proteins. To validate their model they performed site-directed mutagenesis experiments, changing the DNA sequence encoding key amino acid residues and examining the effects on receptor activation profiles for muscone and 34 analogs, some not previously known. They also used a computer simulation method, molecular dynamics, to study the physical movements of the amino acid residues in the receptor to determine their role in odorant binding and to calculate the binding energy for the various musks. These experiments showed that receptor OR5AN1 binds the musk odorants with a hydrogen bond from tyrosine 260 combined with hydrophobic interactions involving phenyalanines 105, 194, and 20; similarly, receptor OR1A1 binds the odorants through interactions with tyrosines 251 and 258 and phenyalanine 206. This work on musk odorant-receptor interactions provide a molecular-level understanding of olfaction and might assist the study of the pharmacological effects of musks.
Block is the Carla Rizzo Delray Distinguished Professor of Chemistry at the University at Albany, State University of New York.  A world authority on the organic chemistry of sulfur and selenium, and particularly the chemistry of genus Allium plants, such as garlic and onions, as well as olfaction, Block is currently a Visiting Scholar working with UCLA organic professor Dr. Ken Houk through June, 2018.