Enzymes from dangerous bacteria turn into important tools for protein chemistry

October 31, 2017 by Ingrid Söderbergh, Umea University

Philipp Ochtrop from Umeå University has worked on a project to turn the two enzymes AnkX and Lem3 from the disease causing bacteria Legionella pneumophila into a valuable tool for the chemical modification of proteins. This new approach for protein functionalization can enable scientists to investigate protein function and develop new drugs against life threatening diseases.

The new technique, which is described in the doctoral thesis of Philipp Ochtrop, is based on an enzymatic reaction called phosphocholination. The phosphocholination is catalyzed by the AnkX, which uses a small organic molecule called CDP-choline to transfers a phosphocholine group to host cell proteins and thereby manipulate its function. The phosphocholination is part of several specific chemical reactions that are used by Legionella pneumophila to overtake a host cell after infection and turn it into a suitable environment for its multiplication. These events consequently lead to the outbreak of severe pneumonia.

"The interesting thing about the chemistry of intracellular bacteria is that it is so different in comparison to human cell's chemistry. This is a unique chance to use enzymes from bacteria in biochemistry, cell biology and biotechnology without having overlapping reactivity with human cells' enzymes," says supervisor Christian Hedberg.

The idea to use AnkX for labeling proteins arose by coincidence during studies on how AnkX modifies certain proteins with phosphocholine. The experiments revealed that AnkX did not care particularly about the three-dimensional structure of its , but only recognized a short in the protein. This discovery lead to the conclusion that any protein could be modified by AnkX, as long as the correct amino acid recognition sequence is added genetically.

"In combination with CDP-choline analogues that we prepared synthetically, the developed strategy can be exploited to reversibly functionalize proteins of interest with an array of useful chemical and biophysical handles", says Philipp Ochtrop.

"A future potential medical use for our results can be the selective labeling of antibodies with specific drugs that are consequently directed to cancer cells and kill them. This approach would be highly beneficial and reduce common side effects that are displayed by conventional cancer therapy."

Philipp Ochtrop has performed his studies in a close and highly interdisciplinary collaboration with a team of researchers led by Professor Aymelt Itzen from the Technical University in Munich.

Explore further: Enzymes from dangerous bacteria become important tools for protein chemistry

More information: Selective protein functionalisation via enzymatic phosphocholination. umu.diva-portal.org/smash/get/ … 47446/FULLTEXT01.pdf

Related Stories

Better cell factories for the drugs of the future

June 23, 2017

Pharmaceuticals based on proteins are promising candidates for the treatment of cancer and other severe diseases, but they can be hard to produce. In a new research project, Chalmers researchers will develop new genetically ...

New insights into bacterial toxins

September 5, 2017

A toxin produced by a bacterium that causes urinary tract infections is related to, yet different in key ways from, the toxin that causes whooping cough, according to new research. The findings, which will be published in ...

Recommended for you

Semimetals are high conductors

March 18, 2019

Researchers in China and at UC Davis have measured high conductivity in very thin layers of niobium arsenide, a type of material called a Weyl semimetal. The material has about three times the conductivity of copper at room ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.