Featured Research

from universities, journals, and other organizations

Enzymatic synthesis of pyrrolysine, the mysterious 22nd amino acid

Date:
November 28, 2011
Source:
Technische Universitaet Muenchen
Summary:
With few exceptions, all known proteins are built up from only twenty amino acids. 25 years ago scientists discovered a 21st amino acid, selenocysteine and ten years ago a 22nd, the pyrrolysine. However, how the cell produces the unusual building block remained a mystery. Now researchers have elucidated the structure of an important enzyme in the production of pyrrolysine.

PylB with methylornithin (3MO) and co-factor S-adenosylmethionine (SAM).
Credit: Felix Quitterer / TUM

With few exceptions, all known proteins are using only twenty amino acids. 25 years ago scientists discovered a 21st amino acid, selenocysteine and ten years ago a 22nd, the pyrrolysine. However, how the cell produces the unusual building block remained a mystery. Now researchers at the Technische Universitaet Muenchen have elucidated the structure of an important enzyme in the production of pyrrolysine.

The scientific journal Angewandte Chemie reports on their results in its "Early View" online section.

Proteins are key players in many vital processes in living organisms.. They transport substances, catalyze chemical reactions, pump ions or recognize signaling molecules. The complexity and variety of proteins is tremendous, in the human body alone there are more than 100,000 different proteins at work. But almost all of them are made up of just twenty different amino acids. Only a few highly specialized proteins additionally contain selenocysteine, the very rare 21st amino acid discovered in 1986.

A big surprise was the discovery of a 22nd amino acid in methane-producing archaea of the family Methanosarcinaceae in 2002: pyrrolysine. It is genetically encoded in a similar manner as that of selenocysteine and the other twenty amino acids. The archaea use the unusual amino acid in proteins that they need for energy conversion. Pyrrolysine is located in the catalytic center of the proteins and is essential for their function. The energy generation process of the archaebacteria would not work without pyrrolysine.

In March 2011, scientists at Ohio State University succeeded in deciphering parts of the manufacturing process of pyrrolysine. They proposed a reaction mechanism suggesting that the enzyme PylB catalyzes the first step of pyrrolysine biosynthesis by converting the amino acid lysine to the intermediate product metyhlornithine. Scientists headed by Michael Groll, Professor of Biochemistry at the TUM-Department of Chemistry, could now determine the crystalline structure of PylB by X-ray using structure analysis.

To their great surprise, they caught the enzyme literally "in the act": at the time of crystallization the reaction product, methylornithine, had not left the enzyme. It adhered to a confined space, a kind of "reaction vessel," still in connection with the centers of the enzyme responsible for its creation. "That the product was still present in the enzyme, was something special and a great stroke of luck," says Felix Quitterer, a member of the scientific staff at the Department of Biochemistry and lead author of the publication. "We were not only able to directly detect the methylornithine, but also retroactively reconstruct how it is created from the source amino acid lysine."

This reaction was not only unknown until now, it is also very difficult to catalyze. It is a cluster of four iron and four sulfur atoms in the active site that is the key to the conversion. "This is a really unusual enzymatic reaction. Up to now no chemist in the laboratory is able to synthesize methylornithine in a one-step reaction starting from lysine," says Michael Groll.

The conversion of lysine to methylornithine is helping scientists to understand how archaebacteria can modify an existing system to enable the formation of a tailored amino acid that, when installed in the appropriate protein, catalyzes a very specific reaction. Researchers can use this knowledge to create artificial amino acids for "custom tailored" enzymes with special properties, that could, for example, find applications in industrial biotechnology and medicine.

A more fundamental reason for the high interest in the synthesis of the 22nd amino acid is that scientists are hoping to find new clues to the evolutionary development of the amino acid-canon. Why does the vast complexity of proteins in living organisms descend from only a few natural amino acids, even though the genetic code would be able to encode many more? An answer on this fundamental question has thus far eluded scientists. Selenocysteine and pyrrolysine are exotic exceptions, but knowledge about their development from the standard amino acids helps to come a little closer to the answer.

This research was funded by the Hans-Fischer-Gesellschaft and the King Abdullah University of Science and Technology as well as the Cluster of Excellence Center for Integrated Protein Science Munich. The measurements were performed at the PXI beamline at the Paul Scherrer Institute (Villigen, Switzerland).


Story Source:

The above story is based on materials provided by Technische Universitaet Muenchen. Note: Materials may be edited for content and length.


Journal Reference:

  1. Felix Quitterer, Anja List, Wolfgang Eisenreich, Adelbert Bacher, Michael Groll. Kristallstruktur der Methylornithin-Synthase (PylB): Einblicke in die Biosynthese von Pyrrolysin. Angewandte Chemie, 2011; DOI: 10.1002/ange.201106765

Cite This Page:

Technische Universitaet Muenchen. "Enzymatic synthesis of pyrrolysine, the mysterious 22nd amino acid." ScienceDaily. ScienceDaily, 28 November 2011. <www.sciencedaily.com/releases/2011/11/111118133052.htm>.
Technische Universitaet Muenchen. (2011, November 28). Enzymatic synthesis of pyrrolysine, the mysterious 22nd amino acid. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2011/11/111118133052.htm
Technische Universitaet Muenchen. "Enzymatic synthesis of pyrrolysine, the mysterious 22nd amino acid." ScienceDaily. www.sciencedaily.com/releases/2011/11/111118133052.htm (accessed July 23, 2014).

Share This




More Plants & Animals News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Michigan Plant's Goal: Flower and Die

Michigan Plant's Goal: Flower and Die

AP (July 22, 2014) An 80-year-old agave plant, which is blooming for the first and only time at a University of Michigan conservatory, will die when it's done (July 22) Video provided by AP
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com
CDC Head Concerned About a Post-Antibiotic Era

CDC Head Concerned About a Post-Antibiotic Era

AP (July 22, 2014) Sounding alarms about the growing threat of antibiotic resistance, CDC Director Tom Frieden warned Tuesday if the global community does not confront the problem soon, the world will be living in a devastating post-antibiotic era. (July 22) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins