Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MIT chemist discovers secret behind nature’s medicines

27.04.2006
MIT scientists have just learned another lesson from nature.

After years of wondering how organisms managed to create self-medications, such as anti-fungal agents, chemists have discovered the simple secret.

Scientists already knew that a particular enzyme was able to coax a reaction out of stubborn chemical concoctions to generate a large family of medically valuable compounds called halogenated natural products. The question was, how do they do it?

Chemists would love to have that enzyme’s capability so they could efficiently reproduce, or slightly re-engineer, those products, which include antibiotics, anti-tumor agents, and fungicides.

Thanks to MIT chemistry Associate Professor Catherine L. Drennan’s recent crystallography sleuthing, the secret to the enzyme’s enviable prowess has come to light and it appears almost anti-climactic. It’s simply a matter of the size of one of its parts. "If an enzyme is a gun that fires to cause a reaction, then we wanted to know the mechanism that pulls the trigger," Drennan said. "In chemistry, we often have to look at ’molecules in, molecules out.’ With halogenated natural products, though, we couldn’t figure out how it happened, because the chemicals are so nonreactive. Now that we have the enzyme’s structure and figured out how it works, it makes sense. But it’s not what we would have predicted."

To make halogenated natural products, enzymes catalyze the transformation of a totally unreactive part of a molecule, in this case a methyl group. They break specific chemical bonds and then replace a hydrogen atom with a halide, one of the elements from the column of the periodic table containing chlorine, bromine and iodine. In the lab, that’s a very challenging task, but nature accomplishes it almost nonchalantly. The trick involves using a turbo-charged enzyme containing iron.

A clue to how these enzymes operate emerged from a 2005 study by Christopher T. Walsh of Harvard Medical School, Drennan’s collaborator and co-author of the study published in the March 16 issue of Nature. Looking at the SyrB2 enzyme that the microorganism Pseudomonas syringae uses to produce the antifungal agent syringomycin, he discovered it had a single iron atom in the protein’s active site, the part responsible for the chemical reaction.

Drennan and her graduate student Leah C. Blasiak, who was first author of the study, crystallized SyrB2 and then used X-ray crystallography to discover the physical structure of the protein. The X-rays scatter off the crystal, creating patterns that can be reconstructed as a three-dimensional model for study.

Normally, iron-containing enzymes have three amino acids that hold the iron in the active site. In this enzyme, however, one of the typical amino acids was substituted with a much shorter one.

That smaller substitute leaves more room in the active site -- enough space for the halide, in this case a chloride ion, to casually slip inside and bind to the iron, without the grand theatrics chemists had anticipated. After the iron and the chloride bind, the protein closes down around the active site, effectively pulling the trigger on the gun.

"We were surprised," Drennan said. "The change in activity required for an enzyme to be capable of catalyzing a halogenation reaction is so radical that people thought there must be a really elaborate difference in their structures. But it’s just a smaller amino acid change in the active site. Things are usually not this simple, but there’s an elegant beauty in this simplicity," and it may be what gives other enzymes the prowess required for making other medicinally valuable halogenated natural products, too.

The research was partially funded by the National Institutes of Health.

Elizabeth A. Thomson | MIT News Office
Further information:
http://www.mit.edu

More articles from Life Sciences:

nachricht Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>