Ready for some weird science? Certain bacteria found in the dirt near coca plants are powered by an enzyme that eats cocaine. Unfortunately, the enzyme breaks down quickly at body temperature, meaning it can’t be used to treat human overdoses or addiction. Now, though, researchers have designed a version that can survive body temps — and more than doubles its cocaine appetite.
Scientists have long been investigating ways to harness cocaine esterase’s drug-chugging power for therapeutic use. It’s been difficult, in part because the naturally occurring enzyme has a 12-minute half-life at human body temperatures. Researchers at the University of Kentucky previously created an improved enzyme with a six-hour half life at body temperature that’s in clinical trials. Now they have upped the ante considerably, with a carefully-designed mutant that can survive over 100 days at body temp. It also dismantles cocaine 150 per cent more efficiently than the wild enzyme.
The team achieved this by building a computer model of the naturally occurring enzyme, and simulating a high-temperature environment to see which part of the structure failed first. Once they determined the weak points, it was just a matter of finding mutations that beefed up those parts of the structure without affecting the enzyme’s activity.
Only two changes were needed: Slight mutations created a double-bond in the weakest region, making a structure that survives at body temp for over 100 days and gnaws through a ton more cocaine. After confirming the structural changes using X-ray crystallography, the team tested the tweaked enzyme in mice.
And man oh man, did it work: According to a recently-published research paper, the modified enzyme fully protected mice from lethal doses of cocaine for at least three days, by far the longest protective effect observed yet. That means the enzyme could be useful both as a short-term antidote, and as a long-term addiction-fighting therapy. Perhaps more importantly, the technique of designing an idealised enzyme is applicable far beyond this one realm.
Obviously, more research is needed. This stuff isn’t coming to your Emergency Room any time in the immediate future. But someday, a drug-hungry enzyme born from bacteria could save someone you know from a cocaine overdose. [ACS Chemical Biology via Slashdot]