We humans have a huge number of different smell receptors, but some of the most famous are the ones that are sensitive to thiols. We don’t miss out on many low oxidation state sulfur compounds: S-alkyl and SH groups reek to the skies as far as our noses are concerned (as do the corresponding selenium compounds). One classic example is ethanol versus ethanethiol, SH for OH on a two-carbon chain. Ethanol smells quite pleasant, even for those of us who don’t drink it, but ethanethiol is something else again. It’s the prototype Sulfur Smell, sort of like what you’d get if someone tried to extinguish a smoldering tractor tire by dumping dead skunks on it. A lot of the lower-molecular-weight thiols fall somewhere on that burning rubber/angry skunk axis, but other delightful notes creep in as well (Major Spill at the Garlic Factory. . .Ah, That’s Why People Don’t Make Hard-Boiled Eggs By Grilling Them In Their Shells. . .Who Left All This Shredded Cabbage Under This Tarp. . .I’ve Eaten Nothing But Raw Broccoli and Green Onions For Six Days Now. . .that sort of thing). Once in a while this can also show up as a drug side effect and there’s not much to be done.
We’ve developed our insane sensitivity to these compounds – the human nose can detect ethanethiol at levels at least one hundred million times lower than we can ethanol, and this effect is used deliberately so that we can smell natural gas leaks. Sulfur compounds like these are the smell of things that will kill us – rotten food, dangerous vapors, probably carnivore excretion/body odors as well. Evolutionarily, there’s clearly been a very strong selection pressure away from such substances, and we’re descended from a long, long time of creatures that put time and effort into avoiding them. But how does that sensitivity work?
This new paper has an interesting answer: copper atoms. Robert Crabtree had proposed this mechanism years ago, and it appears that he’s right. The OR2T11 receptor, known to be sensitive to short-chain thiols, seems to have a very pronounced dependence on copper for it to work at all. A close look at its structure shows two very likely metal binding sites near its receptor pocket as well, and NMR experimental results are consistent with the mechanism. Not all the thiol receptors show this copper effect (human odor sensing is very complex), but this one certainly does.