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 Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>